title: Decline in arylsulfatase B and Increase in chondroitin 4-sulfotransferase combine to increase chondroitin 4-sulfate in traumatic brain injury.
abstract: In an established rat model of penetrating ballistic-like brain injury (PBBI), arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) activity was significantly reduced at the ipsilateral site of injury, but unaffected at the contralateral site or in sham controls. In addition, the ARSB substrate chondroitin 4-sulfate (C4S) and total sulfated glycosaminoglycans increased. The mRNA expression of chondroitin 4-sulfotransferase 1 (C4ST1; CHST11) and the sulfotransferase activity rose at the ipsilateral site of injury (PBBI-I), indicating contributions from both increased production and reduced degradation to the accumulation of C4S. In cultured, fetal rat astrocytes, following scratch injury, the ARSB activity declined and the nuclear hypoxia inducible factor-1α increased significantly. In contrast, sulfotransferase activity and chondroitin 4-sulfotransferase expression increased following astrocyte exposure to TGF-β1, but not following scratch. These different pathways by which C4S increased in the cell preparations were both evident in the response to injury in the PBBI-I model. Hence, findings support effects of injury because of mechanical disruption inhibiting ARSB and to chemical mediation by TGF-β1 increasing CHST11 expression and sulfotransferase activity. The increase in C4S following traumatic brain injury is because of contributions from impaired degradation and enhanced synthesis of C4S which combine in the pathogenesis of the glial scar. This is the first report of how two mechanisms contribute to the increase in chondroitin 4-sulfate (C4S) in TBI. Following penetrating ballistic-like brain injury in a rat model and in the scratch model of injury in fetal rat astrocytes, Arylsulfatase B activity declined, leading to accumulation of C4S. TGF-β1 exposure increased expression of chondroitin 4-sulfotransferase. Hence, the increase in C4S in TBI is attributable to both impaired degradation and enhanced synthesis, combining in the pathogenesis of the glial scar.
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.|Jesse Brown VA Medical Center, Chicago, Illinois, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.|Jesse Brown VA Medical Center, Chicago, Illinois, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Feferman
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.affiliation: Jesse Brown VA Medical Center, Chicago, Illinois, USA.|Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.|Oregon Health and Science University, Portland, Oregon, USA.|VA Portland Health Care System, Portland, Oregon, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Guizzetti
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.|Jesse Brown VA Medical Center, Chicago, Illinois, USA.
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Tobacman
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000096:biosynthesis*; D005260:Female; D008297:Male; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015238:Sulfotransferases / Q000096:biosynthesis*
chemical_list: D002809:Chondroitin Sulfates; D015238:Sulfotransferases; C019893:chondroitin 4-sulfotransferase; D020051:N-Acetylgalactosamine-4-Sulfatase
keywords: CHST11; arylsulfatase B; astrocytes; chondroitin 4-sulfate; glycosaminoglycans; neurocan