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

Heep, Axel; Stoffel‐Wagner, Birgit; Bartmann, Peter; Benseler, Susanne M.; Schaller, Carlo; Groneck, Peter; Obladen, Michael; Felderhoff‐Mueser, Ursula

doi:10.1203/01.pdr.0000141524.32142.53

Cited by 68 publications

(59 citation statements)

References 42 publications

(45 reference statements)

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“…All CSF samples were immediately centrifuged after sampling and stored at -40°C before analysis. To exclude a confounding effect of protein denaturation after a storage time of Ͼ3 y aliquots of CSF samples of seven patients were analyzed for IL-6 concentrations for a second time (28). Correlation analysis (Pearson test; SPSS Inc., Chicago, IL) did not reveal a difference between the two measurements (correlation coefficient, 0.96; p ϭ 0.0001).…”

Section: Methodsmentioning

confidence: 99%

Interleukin-1β, Interleukin-18, and Interferon-γ Expression in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus—Markers of White Matter Damage?

et al. 2007

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Posthemorrhagic hydrocephalus (PHHC) represents a major complication of preterm birth. The aim of this study was to determine whether cerebrospinal fluid (CSF) levels of the proinflammatory cytokines IL-1␤, IL-18, and interferon (IFN)-␥ are altered in the CSF of preterm infants with PHHC and may serve as a marker of white matter damage (WMD). Twenty-seven preterm infants with PHHC were included in the study; 13 of them had signs of cystic WMD (cWMD) on ultrasound examinations. CSF sample 1 was obtained at first ventriculostomy, sample 2 at shunt implantation. Results were compared with a control group of 20 age-matched patients without neurologic diseases. IL-1␤ concentrations were elevated in CSF sample 1 of PHHC patients without WMD and in sample 1 of patients with cWMD. Concentrations of IL-18 were increased in both samples of patients without WMD and in sample 2 of patients with cWMD. CSF levels of IFN-␥ were elevated in sample 1 of PHHC patients with cWMD. The pro-inflammatory cytokine IL-1␤ and IL-18 levels in the CSF are elevated in patients with PHHC. Higher IFN-␥ levels are detected in a subgroup of patients developing cWMD, indicating its involvement in the pathogenesis of cWMD in the context of PHHC. H ydrocephalus following IVH represents a major complication of preterm birth and may result in adverse neurologic outcome in later life. IVH is associated with damage to the white matter, which is exacerbated by hydrocephalus (1). Pressure, distortion, ischemia, and inflammation seem to contribute to this process (2). Although shunting CSF is often an effective treatment, it may prevent only some of the neurologic changes. The identification of mechanisms, mediators, and markers of hydrocephalus appears critical to improve the treatment and prevention of neurologic disability caused by hydrocephalus and associated WMD.It is now widely accepted that immune and inflammatory processes take place in the brain in response to diverse insults such as infection, neurodegenerative disorders, trauma, hemorrhage, and hypoxia-ischemia (3-5). Brain inflammation is characterized by infiltration of circulating immune cells and by activation of resident cells, including microglia. These cells can express, release, and respond to inflammatory mediators. In the CNS, one of the most widely studied is the proinflammatory cytokine IL-1␤. In the immature brain, caspase-1, which is responsible for cleavage of the proinflammatory cytokines IL-1␤ and IL-18 into their biologically active forms, seems to be an important mediator of brain injury (6). There is extensive evidence of direct involvement of IL-1␤ in adult and also in developmental brain injury (7-11). The next member of the IL-1 family, previously designated "IFN-␥ inducing factor," has many properties similar to IL-1␤. To date, only few studies have addressed the function of IL-18 in the context of injury to the immature CNS. Data from animal experiments indicate that IL-18 has an influence on the development of WMD in the immature brain (12). IL-18 itself ma...

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Section: Methodsmentioning

confidence: 99%

Interleukin-1β, Interleukin-18, and Interferon-γ Expression in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus—Markers of White Matter Damage?

et al. 2007

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“…The MR spectroscopic results of some researchers have indicated compromised energy metabolism and suggested the occurrence of cerebral ischemia in experimental hydrocephalus (17). Certain researchers have noted that VEGF was highly expressed in the CSF of premature infants with posthemorrhagic hydrocephalus (18), and VEGF and TGF-β 1 are highly expressed in the CSF of premature infants with posthemorrhagic hydrocephalus (31). HGF is a multipotent growth factor that has mitogenic and morphogenic effects on various epithelial cells.…”

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Expression of HGF and VEGF in the cerebral tissue of adult rats with chronic hydrocephalus after subarachnoid hemorrhage

Chu¹

2011

Mol Med Report

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“…Excessive vascular leak is observed in NEC and IVH, and abnormal blood vessel formation is observed in ROP. Increased concentrations of VEGF are found in IVH (21), in cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus (PHH) (22), and in ROP (23). Increased angiopoietin-2 is observed in IVH (21).…”

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Correlation of 2-Methoxyestradiol Levels in Cord Blood and Complications of Prematurity

et al. 2010

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2-methoxyestradiol (2ME2) is a potent antiangiogenic molecule that inhibits the expression of hypoxia-inducible factor (HIF)-1␣ and, consequently, of VEGF and other HIF-1␣ target genes. Although 2ME2 is elevated during pregnancy in maternal serum, its presence in fetal fluids and its impact in neonatal health are unknown. In this study, we 1) described normal levels of 2ME2 in maternal blood, cord blood, breast milk, and amniotic fluid, and 2) compared a composite measure of perinatal outcome between infants born with high and low levels of 2ME2. We found that 2ME2 was significantly decreased in all fluids compared with prepartum maternal serum. After stratifying babies by 2ME2 exposure levels, we observed no differences in the vulnerability to impaired lung development or to complications involving aberrant angiogenesis or vascular leak, such as necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), posthemorrhagic hydrocephalus (PHH), and retinopathy of prematurity (ROP). In summary, fetal 2ME2 concentrations do not appear to affect neonatal outcome.

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

Cited by 68 publications

References 42 publications

Interleukin-1β, Interleukin-18, and Interferon-γ Expression in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus—Markers of White Matter Damage?

Interleukin-1β, Interleukin-18, and Interferon-γ Expression in the Cerebrospinal Fluid of Premature Infants with Posthemorrhagic Hydrocephalus—Markers of White Matter Damage?

Expression of HGF and VEGF in the cerebral tissue of adult rats with chronic hydrocephalus after subarachnoid hemorrhage

Correlation of 2-Methoxyestradiol Levels in Cord Blood and Complications of Prematurity

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