Partial functional recovery after complete spinal cord transection by combined chondroitinase and clenbuterol treatment.
Spinal cord injury not only disrupts axonal tracts but also causes gliotic, fibrotic, and Schwannotic scarring with resulting deposition of chondroitin sulfate proteoglycans (CSPGs) which prevent axonal reconnection and recovery of locomotor function. Here, we determined whether recovery of locomotor function could be promoted after complete transection, by degrading CSPGs enzymatically within the injury site with chondroitinase ABC (chABC) together with treatment with the beta(2)-adrenoceptor agonist, clenbuterol, a neuroprotective agent which can promote regrowth of lower motoneurons. Partial recovery of locomotor function was observed 8-12 weeks postinjury only after combined chABC and clenbuterol treatment. The recovery of locomotor function coincided with the presence of axons caudal to the injury site arising from neurons of the reticular, vestibular, and red nuclei also only with combined chABC and clenbuterol treatment. Axons myelinated by Schwann cells were most prominent in the transection site in the combined treatment group. Clenbuterol treatment activated cAMP response element binding protein within retrogradely traced neurons which has been associated with axonal regrowth. ChABC treatment decreased scarring due to both CSPG and collagen deposition as well as the gap between intact regions of the spinal cord. ChABC also increased numbers of phagocytic cells which remove myelin debris as well as populations of astrocytes thereby aiding blood-spinal cord barrier reformation. Together the results suggest that chABC and clenbuterol can act synergistically to promote recovery of locomotor function.
Bai
Fusheng
F
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Peng
Hong
H
Etlinger
Joseph D
JD
Zeman
Richard J
RJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001369:Axons / Q000187:drug effects; D019765:Chondroitin ABC Lyase / Q000494:pharmacology / Q000627:therapeutic use*; D002976:Clenbuterol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008124:Locomotion / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013904:Thoracic Vertebrae
D000318:Adrenergic beta-Agonists; D019765:Chondroitin ABC Lyase; D002976:Clenbuterol