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Cell-free oxidized ...
Cell-free oxidized hemoglobin drives reactive oxygen species production and pro-inflammation in an immature primary rat mixed glial cell culture
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- Agyemang, Alex Adusei (författare)
- Lund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Neonatology,Lund University Research Groups
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- Kvist, Suvi Vallius (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neonatologi,Forskargrupper vid Lunds universitet,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Neonatology,Lund University Research Groups
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- Brinkman, Nathan (författare)
- CSL Behring, US
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- Gentinetta, Thomas (författare)
- CSL Behring, Switzerland
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- Illa, Miriam (författare)
- University of Barcelona
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- Ortenlöf, Niklas (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Holmqvist, Bo (författare)
- ImaGene-iT
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- Ley, David (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neonatologi,Forskargrupper vid Lunds universitet,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Neonatology,Lund University Research Groups
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- Gram, Magnus (författare)
- Lund University,Lunds universitet,Neonatologi,Forskargrupper vid Lunds universitet,Sjukdomsorsakande oxidation,Neonatology,Lund University Research Groups,Redox Medicine
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(creator_code:org_t)
- 2021-02-11
- 2021
- Engelska.
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 18:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://jneuroinflam...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with deposition of redox active cell-free hemoglobin (Hb), derived from hemorrhagic cerebrospinal fluid (CSF), in the cerebrum and cerebellum. In a recent study, using a preterm rabbit pup model of IVH, intraventricularly administered haptoglobin (Hp), a cell-free Hb scavenger, partially reversed the damaging effects observed following IVH. Together, this suggests that cell-free Hb is central in the pathophysiology of the injury to the immature brain following GM-IVH. An increased understanding of the causal pathways and metabolites involved in eliciting the damaging response following hemorrhage is essential for the continued development and implementation of neuroprotective treatments of GM-IVH in preterm infant.METHODS: We exposed immature primary rat mixed glial cells to hemorrhagic CSF obtained from preterm human infants with IVH (containing a mixture of Hb-metabolites) or to a range of pure Hb-metabolites, incl. oxidized Hb (mainly metHb with iron in Fe3+), oxyHb (mainly Fe2+), or low equivalents of heme, with or without co-administration with human Hp (a mixture of isotype 2-2/2-1). Following exposure, cellular response, reactive oxygen species (ROS) generation, secretion and expression of pro-inflammatory cytokines and oxidative markers were evaluated.RESULTS: Exposure of the glial cells to hemorrhagic CSF as well as oxidized Hb, but not oxyHb, resulted in a significantly increased rate of ROS production that positively correlated with the rate of production of pro-inflammatory and oxidative markers. Congruently, exposure to oxidized Hb caused a disintegration of the polygonal cytoskeletal structure of the glial cells in addition to upregulation of F-actin proteins in microglial cells. Co-administration of Hp partially reversed the damaging response of hemorrhagic CSF and oxidized Hb.CONCLUSION: Exposure of mixed glial cells to oxidized Hb initiates a pro-inflammatory and oxidative response with cytoskeletal disintegration. Early administration of Hp, aiming to minimize the spontaneous autoxidation of cell-free oxyHb and liberation of heme, may provide a therapeutic benefit in preterm infant with GM-IVH.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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