Inhibiting cell proliferation during formation of the glial scar: effects on axon regeneration in the CNS

• Published in: Neuroscience Vol. 120; no. 1; pp. 41 - 56
• Main Authors: Rhodes, K.E, Moon, L.D.F, Fawcett, J.W
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2003; Elsevier
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; araC; Axons - drug effects; Axons - physiology; Biological and medical sciences; Cell Count - methods; Cell Division - drug effects; Cell Division - physiology; Central Nervous System - cytology; Central Nervous System - drug effects; Central Nervous System - physiology; chondroitin sulphate proteoglycans; Cicatrix - drug therapy; Cicatrix - pathology; Development. Senescence. Regeneration. Transplantation; Fundamental and applied biological sciences. Psychology; Growth Inhibitors - pharmacology; Growth Inhibitors - therapeutic use; Male; microglia; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Neuroglia - cytology; Neuroglia - drug effects; Neuroglia - physiology; NG2; nigrostriatal lesion; oligodendrocyte precursor cells; Oligodendroglia - cytology; Oligodendroglia - drug effects; Oligodendroglia - physiology; Rats; Rats, Sprague-Dawley; Vertebrates: nervous system and sense organs; A; dpl; OP; CS-PG; RT; TBS; MFB; TXTBS; chondroitin sulphate proteoglycans; GAG; L; ECM; GFAP; TSP; oligodendrocyte precursor cells; GAP43; nigrostriatal lesion; TH; V; NG2; TNS; NGS; microglia; araC; Cell proliferation; Proteoglycan; Glial cell; Rat; Neuroglia; Scar; Rodentia; Central nervous system; Axon; Regeneration; Vertebrata; Mammalia; Chondroitin sulfate
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00285-9

Following a CNS lesion many glial cell types proliferate and/or migrate to the lesion site, forming the glial scar. The majority of these cells express chondroitin sulphate proteoglycans (CS-PGs), previously shown to inhibit axonal growth. In this study, in an attempt to diminish glial scar formation and improve axonal regeneration, proliferating cells were eliminated from the lesion site. Adult rats received a continuous infusion of 2% cytosine-D-arabinofuranoside (araC) or saline for 7 days over the lesion site, immediately following a unilateral transection of the right medial forebrain bundle. Additional groups of rats that received subdural infusions prior to the lesion, and lesioned rats which received no infusion, were also compared in the analyses. Animals were killed at 4, 7, 12 or 18 days post-lesion (dpl) and immunohistochemistry was used to determine the effects of these treatments on tyrosine hydroxylase (TH) +-lesioned axons, and on the injury response of glial cells. Almost complete elimination of NG2 + oligodendrocyte progenitor cells from the lesion site was seen up to 7 dpl in araC-infused animals; reduced numbers of reactive CD11b + microglia were also seen but no effects were seen on the injury response of GFAP + astrocytes. Significantly more TH + axons were seen distal to the lesion in araC-treated brains, but these numbers dwindled by 18 dpl.