Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?
Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?
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DOI：
10.1007/s12975-017-0539-1
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发表时间：
2017-06-10
影响因子：
6.9
通讯作者：
Ley D
中科院分区：
文献类型：
--
作者：
Agyemang AA;Sveinsdóttir K;Vallius S;Sveinsdóttir S;Bruschettini M;Romantsik O;Hellström A;Smith LEH;Ohlsson L;Holmqvist B;Gram M;Ley D
小脑体积减小与极早产儿脑室内出血（IVH）有关，可能是神经发育障碍的主要组成部分。来自蛛网膜下腔的血液制品在小脑的沉积被认为是IVH后小脑发育不全的原因机制。采用早产兔仔IVH模型，我们评估了E29（足月前3天）诱导IVH对足月出生后第0天（P0）、足月出生后第2天（P2）和足月出生后第5天（P5）小脑发育的影响。此外，小脑组织中无细胞血红蛋白（Hb）的存在被表征，无细胞Hb被评估为早产IVH后小脑损伤发展的一个因果因素。IVH与外颗粒层（EGL）增生减少（ki67阳性）、浦肯野细胞成熟延迟、小脑白质小胶质细胞活化有关。在IVH幼崽中，P0时小脑的免疫标记表明无细胞Hb广泛存在，主要分布在白质和分子层。脑室内注射Hb清道夫触珠蛋白（Hp）导致免疫标记的Hp在小脑中的相应分布，并部分逆转了IVH后观察到的损伤作用。结果表明，无细胞Hb与IVH后的小脑损伤有因果关系，阻断无细胞Hb可能具有保护作用。本文的在线版本（doi:10.1007/s12975-017-0539-1）包含补充材料，仅供授权用户使用。
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. The online version of this article (doi:10.1007/s12975-017-0539-1) contains supplementary material, which is available to authorized users.
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DOI：
10.1038/jcbfm.2010.137
发表时间：
2010-11
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
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影响因子：
3.7
作者：
Limperopoulos, Catherine;Chilingaryan, Gevorg;du Plessis, Adre J.
通讯作者：
du Plessis, Adre J.
影响因子：
4.7
作者：
Galea J;Cruickshank G;Teeling JL;Boche D;Garland P;Perry VH;Galea I
通讯作者：
Galea I
影响因子：
2.3
作者：
Chintagari, Narendranath Reddy;Julia Nguyen;Alayash, Abdu I.
通讯作者：
Alayash, Abdu I.
影响因子：
1.7
作者：
Kitai, Yukihiro;Hirai, Satori;Arai, Hiroshi
通讯作者：
Arai, Hiroshi