Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oligodendrocyte (OL) progenitor cells are particularly susceptible to perinatal hypoxia/ischemia (H-I) resulting in decreased myelination and attenuated development of white matter fiber tracts. Brevican is an aggregating chondroitin sulfate proteoglycan (CSPG) secreted by OLs and their progenitors prior to and during active developmental myelination whereas neuron-glia antigen 2 (NG2) is a transmembrane CSPG produced by early OL progenitors. Although both proteoglycans are associated with maturation of OLs, it is not known if they are altered by H-I brain injury in the neonate. We have therefore examined the time course of changes in brevican and NG2 abundance and proteolysis in the neonatal rat hippocampus after H-I. In a standard H-I model of unilateral carotid artery ligation and exposure to hypoxia, a cavitary infarct involving the ipsilateral parietal and temporal regions of cerebral cortex, hippocampus, and striatum of most rat pups was clearly evident 4 days after H-I. The abundance of total extractable brevican was markedly reduced in the ipsilateral hippocampus at 1 and 14 days after H-I (relative to the contralateral side). At these times, the total G1 proteolytic fragment of brevican was lower in the ipsilateral hippocampus and the level of a protease-generated brevican fragment was significantly diminished in the OL-rich hippocampal fimbria. Hippocampal NG2 levels were also lower at 1 and 4 days after H-I, but were not different from the contralateral side at 14 days. Since brevican, brevican G1 fragment, and NG2 loss occur around the time of progressive cell death and the appearance of the infarct, it may be that H-I rapidly induces a cellular response that actively depletes these proteoglycans from the hippocampal matrix. While the mechanism of this loss is unclear, it would appear to be an early event in the process that could be involved in apoptotic cell death and/or tissue injury.
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PMID:The effect of hypoxic-ischemic brain injury in perinatal rats on the abundance and proteolysis of brevican and NG2. 1581 74

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.
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PMID:Versican and brevican are expressed with distinct pathology in neonatal hypoxic-ischemic injury. 1797 19