title: 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.
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.
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY 10595, USA.
authors.forename: Govindaiah
authors.initials: G
authors.lastname: Vinukonda
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Zia
authors.forename: Bala B R
authors.initials: BB
authors.lastname: Bhimavarapu
authors.forename: Furong
authors.initials: F
authors.lastname: Hu
authors.forename: Michelle
authors.initials: M
authors.lastname: Feinberg
authors.forename: Aqiba
authors.initials: A
authors.lastname: Bokhari
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.forename: Victor A
authors.initials: VA
authors.lastname: Fried
authors.forename: Praveen
authors.initials: P
authors.lastname: Ballabh
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011247:Pregnancy; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D019765:Chondroitin ABC Lyase; D011508:Chondroitin Sulfate Proteoglycans; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: Aggrecan; Brevican; Chondroitin sulfate proteoglycans; Chondroitinase ABC; Myelination; Neuorcan; Oligodendrocyte; Phosphacan; Versican