1. 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.
- Author
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Vinukonda G, Zia MT, Bhimavarapu BB, Hu F, Feinberg M, Bokhari A, Ungvari Z, Fried VA, and Ballabh P
- Subjects
- Age Factors, Animals, Animals, Newborn, Antigens genetics, Antigens metabolism, Cell Proliferation drug effects, Chondroitin ABC Lyase administration & dosage, Chondroitin Sulfate Proteoglycans genetics, Disease Models, Animal, Female, Fetus, Gestational Age, Humans, Infant, Newborn, Male, Motor Activity drug effects, Motor Activity physiology, Myelin Sheath metabolism, Nerve Tissue Proteins metabolism, Oligodendroglia metabolism, Pregnancy, Proteoglycans genetics, Proteoglycans metabolism, Rabbits, Recovery of Function drug effects, Time Factors, Cerebral Hemorrhage metabolism, Cerebral Hemorrhage pathology, Cerebral Hemorrhage physiopathology, Chondroitin Sulfate Proteoglycans metabolism, Gene Expression Regulation, Developmental physiology, Recovery of Function physiology
- Abstract
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., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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