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

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High presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage. / Ley, David; Romantsik, Olga; Vallius, Suvi; Sveinsdóttir, Kristbjörg; Sveinsdóttir, Snjolaug; Agyemang, Alex A.; Baumgarten, Maria; Mörgelin, Matthias; Lutay, Nataliya; Bruschettini, Matteo; Holmqvist, Bo; Gram, Magnus.

In: Frontiers in Physiology, Vol. 7, No. AUG, 330, 03.08.2016.

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T1 - High presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage

AU - Ley, David

AU - Romantsik, Olga

AU - Vallius, Suvi

AU - Sveinsdóttir, Kristbjörg

AU - Sveinsdóttir, Snjolaug

AU - Agyemang, Alex A.

AU - Baumgarten, Maria

AU - Mörgelin, Matthias

AU - Lutay, Nataliya

AU - Bruschettini, Matteo

AU - Holmqvist, Bo

AU - Gram, Magnus

PY - 2016/8/3

Y1 - 2016/8/3

N2 - 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.

AB - 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.

KW - Hemoglobin

KW - Imaging

KW - Immature brain

KW - Intraventricular hemorrhage

KW - Periventricular white matter

KW - Peroxidase activity

KW - Plasticity

UR - http://www.scopus.com/inward/record.url?scp=84988815589&partnerID=8YFLogxK

U2 - 10.3389/fphys.2016.00330

DO - 10.3389/fphys.2016.00330

M3 - Article

C2 - 27536248

AN - SCOPUS:84988815589

VL - 7

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

IS - AUG

M1 - 330

ER -