Short-term effects of erythropoietin on neurodevelopment in infants with cerebral palsy: A pilot study

Lee, Hee Song; Song, Jung‐Min; Min, Kyunghoon; Choi, Yong‐Soo; Kim, Sun Mi; Cho, Sung Rae; Kim, Min Young

doi:10.1016/j.braindev.2013.11.002

Cited by 17 publications

(14 citation statements)

References 29 publications

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“…These protective effects of Epo during ischemia/ reperfusion and prenatal brain development have prompted the use of recombinant Epo and Epo mimetics in other brain injury models (83, 84) along with transient stroke and traumatic brain injury animal models, such as autoimmune encephalitis (85), intracerebral hemorrhage (86), spinal cord injury (87, 88), neonatal focal stroke (89-92), neonatal hypoxia-ischemia (90, 93-95), intraventricular hemorrhage or periventricular leukomalacia (96) in preterm infants and cerebral palsy (97). These studies demonstrate that high dose systemic recombinant Epo, and Epo mimetics, are safe (98), and can penetrate the blood brain barrier with resulting reduction in histological damage and improvement in function.…”

Section: Epo For Neuroprotectionmentioning

confidence: 99%

“…Phase I/II studies to evaluate feasibility, safely and establish appropriate dosing in human preterm (97, 99, 100) and term neonates (99, 101-103) have been done. Target populations include neonates at high risk for poor neurodevelopmental outcomes due to extreme prematurity, hypoxic ischemic encephalopathy, perinatal stroke, or complex cyanotic heart disease.…”

Section: Epo In Clinical Trialsmentioning

confidence: 99%

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Erythropoietin: Emerging Role of Erythropoietin in Neonatal Neuroprotection

Rangarajan¹,

Juul²

2014

Pediatric Neurology

107

106

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BACKGROUND In the last two decades, there has been considerable evolution in the understanding role of erythropoietin (Epo) in neuroprotection. Epo has both paracrine and autocrine functions in the brain. Epo binding results in neurogenesis, oligodendrogenesis, and angiogenesis. Epo and its receptor are upregulated by exposure to hypoxia and proinflammatory cytokines following brain injury. While Epo aids in recovery of locally injured neuronal cells, it provides negative feedback to glial cells in the penumbra, thereby limiting extension of injury. This forms the rationale for use of recombinant Epo and Epo mimetics in neonatal and adult injury models of stroke, traumatic brain injury, spinal cord injury, intracerebral hemorrhage and neonatal hypoxic-ischemia. METHOD Review of published literature (Pubmed, Medline and Google scholar) RESULTS Preclinical neuroprotective data are reviewed and the rationale for proceeding to clinical trials is discussed. Results from Phase I/II trials are presented, as are updates on ongoing and upcoming clinical trials of Epo neuroprotection in neonatal populations. CONCLUSIONS The scientific rationale and preclinical data for Epo neuroprotection are promising. Phase II and III clinical trials are currently in process to determine the safety and efficacy of neuroprotective dosing of Epo for extreme prematurity and hypoxic ischemic encephalopathy in neonates.

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Section: Epo For Neuroprotectionmentioning

confidence: 99%

Section: Epo In Clinical Trialsmentioning

confidence: 99%

Erythropoietin: Emerging Role of Erythropoietin in Neonatal Neuroprotection

Rangarajan¹,

Juul²

2014

Pediatric Neurology

107

106

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“…[1] Brain damage of prematurity is the predominant form of the acquired brain damage in neonates who undergo neurological morbidity. [2] There are only limited therapies to improve the outcome from the HIBD.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

Zhu

Jiang

2017

Chinese Medical Journal

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Background:Recombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway.Methods:Postnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h. All the rat pups were randomized into five groups as follows: (1) control group; (2) hypoxia-ischemic (HI) group; (3) HI + LY294002 group; (4) HI + rh-EPO group; and (5) HI + rh-EPO + LY294002 group. The phospho-Akt protein was tested 90 min after the whole operation, and CD34, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor (VEGF) were also tested 2 days after the whole operation.Results:In the hypoxic and ischemic zone of the premature rat brain, the rh-EPO induced CD34+ cells to immigrate to the HI brain zone (P < 0.05) and also upregulated the VEGFR2 protein expression (P < 0.05) and VEGF mRNA level (P < 0.05) through the PI3K/Akt (P < 0.05) signaling pathway when compared with other groups.Conclusions:The rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway. Besides, the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.

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“…They have anti-inflammatory and anti-apoptotic properties. 13,14 They are known to improve the cognition in infants. In a study, including preterm infants, it was observed that none of the surviving infants developed CP, while five in the placebo group did.…”

Section: Drugsmentioning

confidence: 99%

Clinical neurorestorative progresses in cerebral palsy

Sharma¹,

Geng²,

Sane³

et al. 2017

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Cerebral palsy (CP), group of permanent nonprogressive clinical disorders in children, is caused by damage to the immature brain. Conventionally available treatments for CP are mainly targeted toward management of its symptoms. With the upcoming field of neurorestorative strategies, we are now able to repair the core brain damage in CP. There are various drugs, stem cells, etc, which have been implicated to have neurorestorative properties. Autologous bone marrow stem cells, umbilical cord stem cells, neural stem cells, and olfactory ensheathing cells have shown the safety and efficacy in preliminary studies. Here, we review the different medicines and cell types that have shown beneficial effects in clinical studies. We propose that combination strategies may be the future of neurorestoration.

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Short-term effects of erythropoietin on neurodevelopment in infants with cerebral palsy: A pilot study

Cited by 17 publications

References 29 publications

Erythropoietin: Emerging Role of Erythropoietin in Neonatal Neuroprotection

Erythropoietin: Emerging Role of Erythropoietin in Neonatal Neuroprotection

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

Clinical neurorestorative progresses in cerebral palsy

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