Versican and brevican are expressed with distinct pathology in neonatal hypoxic-ischemic injury.
The developing brain is uniquely susceptible to injury after exposure to hypoxia-ischemia (H-I). Lecticans are developmentally regulated in formative white matter and exert growth-inhibitory effects in several adult injury models, yet little is known regarding their role in neonatal H-I injury. The main objectives of this study were to examine the expression profiles of brevican and versican in rat using a standard H-I model and to determine whether altered expression was associated with distinct components of white and gray matter pathology. The H-I procedure in postnatal day 7 rats produced progressive injury limited to the ipsilateral hemisphere. Cresyl violet staining revealed severe cavitary infarctions at 14 and 21 days that were absent at 4 days. Cellular damage, as measured by glial fibrillary acidic protein and fractin immunoreactivity, occurred in cortical and subcortical gray matter at all end points. O4 sulfatide immunoreactivity was reduced in the external capsule, hippocampal fimbria, and corpus striatum at 4 days relative to that contralaterally, suggesting the loss of preoligodendrocytes. Brevican expression was reduced in the cortex and hippocampus at 4 days but was markedly elevated at later end points, localizing to regions of cellular damage both in and proximal to the lesion core. However, versican was reduced in the external capsule 4 days after H-I, a reduction that was sustained up to 21 days in white matter. These data demonstrate unique expression profiles for lecticans after neonatal H-I, suggesting brevican deposition is elevated in response to progressive gray matter injury, whereas diminished versican expression may be associated with deep cerebral white matter injury.
Leonardo
Christopher C
CC
Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, College of Medicine, University of South Florida, Tampa, Florida, USA.
Eakin
Autumn K
AK
Ajmo
Joanne M
JM
Gottschall
Paul E
PE
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology; D058581:Brevican; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology*; D037181:Lectins, C-Type / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012273:Ribulose-Bisphosphate Carboxylase / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013433:Sulfoglycosphingolipids / Q000378:metabolism; D053675:Versicans / Q000378:metabolism*
C546939:Bcan protein, rat; D058581:Brevican; D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D013433:Sulfoglycosphingolipids; C508324:Vcan protein, rat; D053675:Versicans; D012273:Ribulose-Bisphosphate Carboxylase