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High presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage

Ley, David LU ; Romantsik, Olga LU ; Vallius, Suvi LU ; Sveinsdóttir, Kristbjörg LU ; Sveinsdóttir, Snjolaug LU ; Agyemang, Alex A. LU ; Baumgarten, Maria LU ; Mörgelin, Matthias LU ; Lutay, Nataliya LU and Bruschettini, Matteo LU , et al. (2016) In Frontiers in Physiology 7(AUG).
Abstract

Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15-20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and... (More)

Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15-20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH. Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 h following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e., not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM) demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH.

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keywords
Hemoglobin, Imaging, Immature brain, Intraventricular hemorrhage, Periventricular white matter, Peroxidase activity, Plasticity
in
Frontiers in Physiology
volume
7
issue
AUG
publisher
Frontiers
external identifiers
  • scopus:84988815589
  • wos:000380791000002
ISSN
1664-042X
DOI
10.3389/fphys.2016.00330
language
English
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yes
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299fa399-f3ca-4199-81a4-bb57b6e0d772
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2016-11-02 09:45:48
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2017-10-01 05:25:13
@article{299fa399-f3ca-4199-81a4-bb57b6e0d772,
  abstract     = {<p>Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15-20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH. Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 h following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e., not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM) demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH.</p>},
  articleno    = {330},
  author       = {Ley, David and Romantsik, Olga and Vallius, Suvi and Sveinsdóttir, Kristbjörg and Sveinsdóttir, Snjolaug and Agyemang, Alex A. and Baumgarten, Maria and Mörgelin, Matthias and Lutay, Nataliya and Bruschettini, Matteo and Holmqvist, Bo and Gram, Magnus},
  issn         = {1664-042X},
  keyword      = {Hemoglobin,Imaging,Immature brain,Intraventricular hemorrhage,Periventricular white matter,Peroxidase activity,Plasticity},
  language     = {eng},
  month        = {08},
  number       = {AUG},
  publisher    = {Frontiers},
  series       = {Frontiers in Physiology},
  title        = {High presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage},
  url          = {http://dx.doi.org/10.3389/fphys.2016.00330},
  volume       = {7},
  year         = {2016},
}