Intraventricular hemorrhage induces deposition of proteoglycans in premature rabbits, but their in vivo degradation with chondroitinase does not restore myelination, ventricle size and neurological recovery.

Intraventricular hemorrhage induces deposition of proteoglycans in premature rabbits, but their in vivo degradation with chondroitinase does not restore myelination, ventricle size and neurological recovery.
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DOI:
10.1016/j.expneurol.2013.02.018
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发表时间:
2013-09
影响因子:
5.3
通讯作者:
Ballabh, Praveen
Ballabh, Praveen
中科院分区:
医学2区
文献类型:
--
作者:
Vinukonda, Govindaiah;Zia, Muhammad T.;Bhimavarapu, Bala B. R.;Hu, Furong;Feinberg, Michelle;Bokhari, Aqiba;Ungvari, Zoltan;Fried, Victor A.;Ballabh, Praveen

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脑室内出血(IVH)会导致早产儿白质损伤和脑积水。硫酸软骨素蛋白多糖(CSPG)——neuorcan、brevican、versican、aggrecan 和 Phosphacan——在脑损伤后在细胞外基质中不受调节,它们的降解增强了大脑的可塑性。因此,我们假设患有 IVH 的早产儿前脑中 CSPG 水平升高,并且 CSPG 的体内降解会促进少突胶质细胞的成熟,增强髓鞘形成,促进神经功能恢复,并最大限度地减少脑积水。我们发现,与对照组相比,患有 IVH 的早产兔幼崽和人类婴儿中神经聚糖、短蛋白聚糖、聚集蛋白聚糖、磷酸聚糖和多功能蛋白聚糖的水平升高,而 NG2 表达降低。脑室内软骨素酶 ABC (ChABC) 降低 neuorcan、brevican、versican 和 aggrecan 的表达,但不降低 NG2。然而,ChABC 治疗并没有促进 IVH 幼崽少突胶质细胞的成熟、髓鞘形成或神经功能恢复。此外,ChABC 并没有减少神经胶质增生或脑室扩大。我们的结果表明,IVH 会引起 CSPG 成分的明显变化,并且通过体内 ChABC 治疗逆转这些变化既不会促进临床恢复、髓鞘形成,也不会减少早产兔幼崽的脑室扩大。
Intraventricular hemorrhage (IVH) results in white matter injury and hydrocephalus in premature infants. Chondroitin sulfate proteoglycans (CSPGs)--neuorcan, brevican, versican, aggrecan and phosphacan—are unregulated in the extracellular matrix after brain injury, and their degradation enhances plasticity of the brain. Therefore, we hypothesized that CSPG levels were elevated in the forebrain of premature infants with IVH and that in vivo degradation of CSPGs would enhance maturation of oligodendrocyte, augment myelination, promote neurological recovery, and minimize hydrocephalus. We found that levels of neurocan, brevican, aggrecan, phosphacan, and versican were elevated, whereas NG2 expression was reduced in premature rabbit pups and human infants with IVH compared to controls. Intracerebroventricular chondroitinase ABC (ChABC) reduced the expression of neuorcan, brevican, versican and aggrecan, but not NG2. However, ChABC treatment did not enhance maturation of oligodendrocytes, myelination, or neurological recovery in the pups with IVH. Moreover, ChABC did not reduce gliosis or ventriculomegaly. Our results demonstrate that IVH induces distinct changes in the components of CSPGs, and that reversing these changes by in vivo ChABC treatment neither promotes clinical recovery, myelination, nor reduces ventriculomegaly in preterm rabbit pups.
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