High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage
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. Curren...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2016.00330/full |
| _version_ | 1818174769836589056 |
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| author | David Ley Olga Romantsik Suvi Vallius Kristbjörg Sveinsdóttir Snjolaug Sveinsdóttir Alex A. Agyemang Maria Baumgarten Matthias Mörgelin Nataliya Lutay Matteo Bruschettini Bo Holmqvist Magnus Gram |
| author_facet | David Ley Olga Romantsik Suvi Vallius Kristbjörg Sveinsdóttir Snjolaug Sveinsdóttir Alex A. Agyemang Maria Baumgarten Matthias Mörgelin Nataliya Lutay Matteo Bruschettini Bo Holmqvist Magnus Gram |
| author_sort | David Ley |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T19:49:40Z |
| format | Article |
| id | doaj.art-ac16b1c2ab7a47e89cc34c5df526551c |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T19:49:40Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ac16b1c2ab7a47e89cc34c5df526551c2022-12-22T00:52:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-08-01710.3389/fphys.2016.00330208362High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular HemorrhageDavid Ley0Olga Romantsik1Suvi Vallius2Kristbjörg Sveinsdóttir3Snjolaug Sveinsdóttir4Alex A. Agyemang5Maria Baumgarten6Matthias Mörgelin7Nataliya Lutay8Matteo Bruschettini9Bo Holmqvist10Magnus Gram11Department of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Infection Medicine, Lund University, Skane University HospitalLund, SwedenDepartment of Clinical Sciences Lund, Infection Medicine, Lund University, Skane University HospitalLund, SwedenImaGene-iT ABLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenImaGene-iT ABLund, SwedenDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Skane University HospitalLund, SwedenSevere 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.https://www.frontiersin.org/article/10.3389/fphys.2016.00330/fullintraventricular hemorrhagehemoglobinperiventricular white matterimmature brainplasticityperoxidase activity |
| spellingShingle | David Ley Olga Romantsik Suvi Vallius Kristbjörg Sveinsdóttir Snjolaug Sveinsdóttir Alex A. Agyemang Maria Baumgarten Matthias Mörgelin Nataliya Lutay Matteo Bruschettini Bo Holmqvist Magnus Gram High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage Frontiers in Physiology intraventricular hemorrhage hemoglobin periventricular white matter immature brain plasticity peroxidase activity |
| title | High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage |
| title_full | High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage |
| title_fullStr | High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage |
| title_full_unstemmed | High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage |
| title_short | High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage |
| title_sort | high presence of extracellular hemoglobin in the periventricular white matter following preterm intraventricular hemorrhage |
| topic | intraventricular hemorrhage hemoglobin periventricular white matter immature brain plasticity peroxidase activity |
| url | https://www.frontiersin.org/article/10.3389/fphys.2016.00330/full |
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