IT Delivery of ChABC Modulates NG2 and Promotes GAP-43 Axonal Regrowth After Spinal Cord Injury

• Published in: Cellular and molecular neurobiology Vol. 31; no. 8; pp. 1129 - 1139
• Main Authors: Novotna, I., Slovinska, L., Vanicky, I., Cizek, M., Radonak, J., Cizkova, D.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.11.2011
• Subjects: Animals; Antigens - metabolism; Axons - drug effects; Axons - pathology; Axons - physiology; Behavior, Animal - physiology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chondroitin ABC Lyase - administration & dosage; Chondroitin ABC Lyase - metabolism; Chondroitin ABC Lyase - pharmacology; Chondroitin Sulfate Proteoglycans - metabolism; GAP-43 Protein - metabolism; Injections, Spinal; Male; Motor Activity - physiology; Nerve Regeneration - drug effects; Neurobiology; Neurosciences; Original Research; Proteoglycans - metabolism; Rats; Rats, Wistar; Spinal Cord - drug effects; Spinal Cord - pathology; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Chondroitinase ABC; Functional recovery; Growth-associated protein-43; Spinal cord injury; Proteoglycan NG2; Axon regeneration
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-011-9714-1

Chondroitin sulphate proteoglycans (CSPGs) with the major component NG2 have an inhibitory effect on regeneration of damaged axons after spinal cord injury. In this study, we investigate whether the digestion of CSPGs by chondroitinase ABC (ChABC) may decrease the NG2 expression and promote axon regrowth through the lesion site. Rats underwent spinal cord compression injury and were treated with ChABC or vehicle through an intrathecal catheter delivery at 2, 3, and 4 days after injury. In addition, animals were behaviorally scored using BBB test in weekly intervals after SCI. Based on immunocytochemical analyses, we have quantified distribution of NG2 glycoprotein and GAP-43 in spinal cord tissue in both experimental groups. Multiple injections of ChABC caused decrease of NG2 expression at lesion site at 5 and 7 days, but not at 14 and 28 days in comparison with vehicle-treated rats and significantly enhanced GAP-43 expression during the entire survival. The densitometry analysis showed significantly higher GAP-43 immunoreactivity (1.8–2.2-fold) in the regrowing axons and cell bodies within the central lesion cavity when compared with vehicle group. Longitudinally oriented and disorganized GAP-43-labeled axons were able to infiltrate and penetrate damaged tissue. The outgrowth of GAP-43 axons after CHABC delivery was significantly longer (≤0.457 mm) when compared with the length of axons in vehicle-treated rats (≤0.046 mm). Present findings suggest that degradation of NG2 with acute IT ChABC treatment may promote ongoing (long-lasting) axonal regenerative processes at late survival (14 and 28 days), but with no significant impact on the improvement of motor function.