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 scar formation in injured cerebral cortex using heparin hexasaccharide (6-mer) and octasaccharide (8-mer). A single injection of 20 microl of heparin 6-mer or heparin 8-mer (10mg/ml), native heparin (10mg/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 marker, 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.
Hayashi
Noriko
N
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Miyata
Seiji
S
Kariya
Yutaka
Y
Takano
Ryo
R
Hara
Saburo
S
Kamei
Kaeko
K
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing / Q000187:drug effects*
C090795:2H6 antigen, human; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D009844:Oligosaccharides; D006493:Heparin