Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus

Koehne, Petra; Hochhaus, Frederike; Felderhoff‐Mueser, Ursula; Ring-Mrozik, E.; Obladen, Michael; Bührer, Christoph

doi:10.1007/s00381-002-0567-2

Cited by 33 publications

(30 citation statements)

References 31 publications

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“…Therefore, identifying additional biomarkers for the early identification of neuronal injury, in addition to cranial ultrasonography, is crucial for improving therapeutic outcomes 27. Various CSF biomarkers, including TGFß‐1 28, VEGF 29, BDNF 20, GDNF 30, and proinflammatory cytokines, such as IL‐1α 31, IL‐1ß 32, CCL‐3, and CCL‐19 31 have been used to diagnose brain injury and predict neurodevelopmental outcomes. In a previous study of brain‐specific proteins in the CSF, glial fibrillary acidic protein level was found to be substantially higher in infants with IVH and PHH than in normal infants.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Ahn

Chang

Sung

et al. 2018

Stem Cells Translational Medicine

121

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We previously demonstrated that transplanting mesenchymal stem cells (MSCs) improved recovery from brain injury induced by severe intraventricular hemorrhage (IVH) in newborn rats. To assess the safety and feasibility of MSCs in preterm infants with severe IVH, we performed a phase I dose‐escalation clinical trial. The first three patients received a low dose of MSCs (5 × 106 cells/kg), and the next six received a high dose (1 × 107 cells/kg). We assessed adverse outcomes, including mortality and the progress of posthemorrhagic hydrocephalus. Intraventricular transplantation of MSCs was performed in nine premature infants with mean gestational age of 26.1 ± 0.7 weeks and birth weight of 808 ± 85 g at 11.6 ± 0.9 postnatal days. Treatment with MSCs was well tolerated, and no patients showed serious adverse effects or dose‐limiting toxicities attributable to MSC transplantation. There was no mortality in IVH patients receiving MSCs. Infants who underwent shunt surgery showed a higher level of interleukin (IL)‐6 in cerebrospinal fluid (CSF) obtained before MSC transplantation in comparison with infants who did not receive a shunt. Levels of IL‐6 and tumor necrosis factor‐α in initially obtained CSF correlated significantly with baseline ventricular index. Intraventricular transplantation of allogeneic human UCB‐derived MSCs into preterm infants with severe IVH is safe and feasible, and warrants a larger, and controlled, phase II study. Stem Cells Translational Medicine 2018;7:847–856

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Ahn

Chang

Sung

et al. 2018

Stem Cells Translational Medicine

121

View full text Add to dashboard Cite

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“…Thirty-five ventricular CSF samples were obtained from 18 premature infants who were admitted for surgical treatment of PHHC after severe IVH. The median birth weight was 676 g, and the median gestational age at birth was 25 Nine of the 18 patients had signs of gross c-WMD on ultrasound at day 28 postnatal age ( Table 2). WMD was defined as single or multiple cystic periventricular leukomalacia or gross cystic white matter defect after hemorrhagic infarction of the periventricular white matter (14).…”

Section: Methodsmentioning

confidence: 99%

Vascular Endothelial Growth Factor and Transforming Growth Factor-β1 Are Highly Expressed in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus

et al. 2004

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“…18 -20 The weak constitutive expression in the adult brain can be rapidly increased by hypoxia and acute metabolic stress as evidenced by detection of EPO in cerebrospinal fluid or postmortem brain tissue after traumatic brain injury, subarachnoid hemorrhage, and stroke. 12,13,[21][22][23][24] Hypoxia-induced expression of EPO and the classical EPOR in brain cells may contribute to ischemic tolerance, 16,25 whereas neutralization of the brain endogenous EPO augments ischemic damage. 4 In fact, EPOR-deficient mice show increased apoptosis in the brain and enhanced hypoxia sensitivity.…”

Section: Epo Signaling In the Nervous Systemmentioning

confidence: 99%

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

et al. 2009

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Summary:The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, antiapoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.

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Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus

Abstract: We conclude that conditions necessitating surgical intervention in hydrocephalus patients result in increased CSF concentrations of VEGF and EPO.

Cited by 33 publications

References 31 publications

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Vascular Endothelial Growth Factor and Transforming Growth Factor-β1 Are Highly Expressed in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

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