Attenuation of glial scar formation in the injured rat brain by heparin oligosaccharides

Injury to the central nervous system causes glial reactions, which eventually lead to the formation of a glial scar and inhibit axonal regeneration. The present Study aimed to reduce the extent of glial seat-formation in injured cerebral cortex using heparin hexasaccharide (6-mer) and octasaccharide (8-mer). A single injection of 20 mul of heparin 6-mer or heparin 8-mer (10 mg/ml), native heparin (10 mg/ml), or saline vehicle was given into the wound cavity just after cryo-injury in the cerebral cortex. In saline-injected control rats, strong chondroitin sulfate-A (CS-A) immunoreactivity using 2H6 antibody was observed around the injured site. Double labeling using an antibody against glial fibrillary acidic protein, a glial market, further demonstrated that CS-A immunoreactivity was mainly expressed on the reactive astrocytes at the glial scar, indicating that CS-A immunohistochemistry is useful for evaluating glial scar formation. Quantitative morphometrical analysis revealed that the area of CS-A immunoreactivity was significantly decreased by 53% in heparin-6-mer-injected animals and 44% in heparin-8-mer-injected ones 6 days after the injury, but native heparin had no effect on CS-A-immunoreactive areas. Both heparin oligosaccharides also attenuated the intensity of CS-A immunoreactivity in the reactive astrocytes and Caused astrocytic cellular processes to be less branched. These results demonstrate that a single injection of heparin oligosaccharides attenuates glial scar formation, indicating that heparin oligosaccharides may be applicable to many fibrotic diseases and restore functional integrity. (C) 2004 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.