Systematic review seeking erythropoietin role for neuroprotection in neonates with hypoxic ischemic encephalopathy: presently where do we stand

Garg, Bhawan Deep; Sharma, Deepak; Bansal, Anju

doi:10.1080/14767058.2017.1366982

Cited by 25 publications

(16 citation statements)

References 41 publications

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“…Following an acute, short hypoxic-ischemic incident, the inflammatory cascade might be less activated, but this is highly speculative. Second, anemic hypoxia during pregnancy and birth stimulates epo production, which might act as a protective mechanism against the adverse effects of asphyxia [17].…”

Section: Discussionmentioning

confidence: 99%

Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia

Kalteren¹,

Horst²,

Heijer³

et al. 2018

Neonatology

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Background: Perinatal anemia may cause perinatal asphyxia. Its pathophysiology and neurodevelopmental effects are theoretically different from other causes of perinatal asphyxia. Objective: The study aimed to determine whether perinatal anemia results in different short-term and long-term outcomes than other causes of perinatal asphyxia treated with therapeutic hypothermia. Methods: We retrospectively included infants with moderate to severe hypoxic-ischemic encephalopathy, born between May 2009 and October 2015. During follow-up, we assessed cognitive and motor development at 2–3 years of age, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Neurodevelopmental outcome (NDO) was classified as abnormal in case of cerebral palsy with Gross Motor Function Classification System ≥III and/or a BSID-III composite score < 85. Outcomes of infants with perinatal anemia (initial hemoglobin < 7 mmol/L) were compared to infants born with perinatal asphyxia due to other causes. Results: In total, 111 infants were included of whom 30 infants (27%) died during the neonatal period. Infants with anemia (n = 23) had a higher mortality risk, OR 3.33, 95% CI 1.27–8.72, p = 0.01. None of the surviving infants with anemia (n = 12) had an abnormal NDO, in contrast to 26/69 (38%) with neurodevelopmental impairments, particularly motor problems, in the non-anemic group, p < 0.01. Conclusions: Perinatal anemia causing moderate to severe perinatal asphyxia is associated with a higher risk for neonatal mortality. All survivors with perinatal anemia, however, showed a normal NDO in contrast to children who were born asphyxiated due to other causes. The underlying pathophysiological mechanism for the favorable NDO in the perinatal anemia group needs further elucidation.

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Section: Discussionmentioning

confidence: 99%

Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia

Kalteren¹,

Horst²,

Heijer³

et al. 2018

Neonatology

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“…At 3 months-of-age, there were no significant differences between the groups in terms of their neuromuscular function or their brain score after MRI. A limitation for both studies is the relatively small sample size, and the use of a single dose of r-Hu-EPO in the latter study [121].…”

Section: Clinical Studies On Neonatal Hypoxic-ischemic Encephalopathymentioning

confidence: 99%

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Oorschot

Sizemore

Amer

2020

IJMS

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Perinatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of morbidity and mortality. Moderate hypothermia (33.5 °C) is currently the sole established standard treatment. However, there are a large number of infants for whom this therapy is ineffective. This inspired global research to find neuroprotectants to potentiate the effect of moderate hypothermia. Here we examine erythropoietin (EPO) as a prominent candidate. Neonatal animal studies show that immediate, as well as delayed, treatment with EPO post-injury, can be neuroprotective and/or neurorestorative. The observed improvements of EPO therapy were generally not to the level of control uninjured animals, however. This suggested that combining EPO treatment with an adjunct therapeutic strategy should be researched. Treatment with EPO plus hypothermia led to less cerebral palsy in a non-human primate model of perinatal asphyxia, leading to clinical trials. A recent Phase II clinical trial on neonatal infants with HIE reported better 12-month motor outcomes for treatment with EPO plus hypothermia compared to hypothermia alone. Hence, the effectiveness of combined treatment with moderate hypothermia and EPO for neonatal HIE currently looks promising. The outcomes of two current clinical trials on neurological outcomes at 18–24 months-of-age, and at older ages, are now required. Further research on the optimal dose, onset, and duration of treatment with EPO, and critical consideration of the effect of injury severity and of gender, are also required.

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“…Hypoxic-ischemic encephalopathy (HIE) is characterized with ischemic-induced brain damage and may cause neuropsychiatric symptoms (Grasso et al 2015). In developing countries, HIE is one of the leading causes of neonatal mortality and may lead to neurodevelopmental disability in later life (Garg et al 2017). Current therapies for HIE, including mild hypothermia, hyperbaric oxygen, positive pressure ventilation and blood purification, are all physical in nature; however, few drugs are available.…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin protects neurons from apoptosis via activating PI3K/AKT and inhibiting Erk1/2 signaling pathway

Wei

Wang

et al. 2019

3 Biotech

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The aim of this study was to explore the neuroprotective effect and the underlying mechanism of erythropoietin (EPO) on the cortical neuronal cells insulted with oxygen and glucose deprivation (OGD). Different concentrations of EPO were used to determine the anti-apoptosis effect of EPO. In addition, PI3K inhibitor LY294002 and ERK1/2 inhibitor U0126 were added to explore the underlying mechanism of EPO. Cell apoptosis rate was measured by flow cytometry. The protein expression of Bax, Bcl-2, cleaved caspase-3, AKT, p-AKT, Erk1/2 and p-Erk1/2 wasmeasured by Western blot. Our results showed that EPO alleviates OGD-induced cell apoptosis in a dose-dependent manner; the neuroprotective effect of EPO was further confirmed by the fact that EPO treatment reversed the protein expression of cleaved caspase-3, as well as the Bcl-2/ Bax ratio as compared with the OGD treatment. In the mechanism part, our results demonstrated that OGD and EPO nearly had no influence on the protein expression of AKT and Erk1/2 but altered the phosphorylation of them. Specifically, OGD decreased the expression of p-AKT and increased the expression of p-Erk1/2; while, EPO treatment reversed the expression of p-AKT and p-Erk1/2 as compared with OGD treatment. Interestingly, LY294002 decreased the expression of p-AKT and attenuated the neuroprotective effect of EPO; while, U0126 decreased the expression of p-Erk1/2 and enhanced the neuroprotective effect of EPO. Our study demonstrated that EPO protects neurons against apoptosis induced by OGD, which is closely related with activation of PI3K/AKT and inactivation of Erk1/2 signaling pathway.

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Systematic review seeking erythropoietin role for neuroprotection in neonates with hypoxic ischemic encephalopathy: presently where do we stand

Abstract: EPO treatment has neuroprotective effects against moderate/severe HIE and improves long-term behavioral neurological developments in neonates.

Cited by 25 publications

References 41 publications

Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia

Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Erythropoietin protects neurons from apoptosis via activating PI3K/AKT and inhibiting Erk1/2 signaling pathway

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