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Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage : Causal in Cerebellar Damage?

Agyemang, Alex Adusei LU ; Sveinsdóttir, Kristbjörg LU ; Vallius, Suvi LU ; SVEINSDOTTIR, SNJOLAUG LU ; Bruschettini, Matteo LU ; Romantsik, Olga LU ; Hellström, Ann LU ; Smith, Lois E. H.; Ohlsson, Lennart LU and Holmqvist, Bo, et al. (2017) In Translational Stroke Research p.1-13
Abstract

Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the... (More)

Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.

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published
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keywords
Cerebellum, External granular layer, Haptoglobin, Hemoglobin, Intraventricular hemorrhage
in
Translational Stroke Research
pages
13 pages
publisher
Springer
external identifiers
  • scopus:85020660654
ISSN
1868-4483
DOI
10.1007/s12975-017-0539-1
language
English
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yes
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b6e285e3-b26b-4610-bc3b-0f086d7a62f7
date added to LUP
2017-08-11 15:51:45
date last changed
2017-08-24 14:12:31
@article{b6e285e3-b26b-4610-bc3b-0f086d7a62f7,
  abstract     = {<p>Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.</p>},
  author       = {Agyemang, Alex Adusei and Sveinsdóttir, Kristbjörg and Vallius, Suvi and SVEINSDOTTIR, SNJOLAUG and Bruschettini, Matteo and Romantsik, Olga and Hellström, Ann and Smith, Lois E. H. and Ohlsson, Lennart and Holmqvist, Bo and Gram, Magnus and Ley, David},
  issn         = {1868-4483},
  keyword      = {Cerebellum,External granular layer,Haptoglobin,Hemoglobin,Intraventricular hemorrhage},
  language     = {eng},
  month        = {06},
  pages        = {1--13},
  publisher    = {Springer},
  series       = {Translational Stroke Research},
  title        = {Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage : Causal in Cerebellar Damage?},
  url          = {http://dx.doi.org/10.1007/s12975-017-0539-1},
  year         = {2017},
}