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.