Mats made from fibronectin support oriented growth of axons in the damaged spinal cord of the adult rat.
A variety of biological as well as synthetic implants have been used to attempt to promote regeneration into the damaged spinal cord. We have implanted mats made from fibronectin (FN) into the damaged spinal cord to determine their effectiveness as a substrate for regeneration of axons. These mats contain oriented pores and can take up and release growth factors. Lesion cavities 1 mm in width and depth and 2 mm in length were created on one side of the spinal cord of adult rats. FN mats containing neurotrophins or saline were placed into the lesion. Mats were well integrated into surrounding tissue and showed robust well-oriented growth of calcitonin gene-related peptide, substance P, GABAergic, cholinergic, glutamatergic, and noradrenergic axons into FN mats. Transganglionic tracing using cholera toxin B indicated large-diameter primary afferents had grown into FN implants. Schwann cells had also infiltrated FN mats. Electron microscopy confirmed the presence of axons within implants sites, with most axons either ensheathed or myelinated by Schwann cells. Mats incubated in brain-derived neurotrophic factor and neurotrophin-3 showed significantly more neurofilament-positive and glutamatergic fibers compared to saline- and nerve growth factor-incubated mats, while mats incubated with nerve growth factor showed more calcitonin gene-related peptide-positive axons. In contrast, neurotrophin treatment had no effect on PGP 9.5-positive axons. In addition, in some animals with neurotrophin-3-incubated mats, cholera toxin B-labelled fibers had grown from the mat into adjoining intact areas of spinal cord. The results indicate that FN mats provide a substrate that is permissive for robust oriented axonal growth in the damaged spinal cord, and that this growth is supported by Schwann cells.
King
Von R
VR
Department of Neuroscience, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary University of London, Mile End Road, E1 4NS, London, UK. Vonrking@yahoo.co.uk
Henseler
Manuel
M
Brown
Robert A
RA
Priestley
John V
JV
D020341:Absorbable Implants; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D004343:Drug Implants; D004357:Drug Synergism; D005353:Fibronectins / Q000008:administration & dosage* / Q000737:chemistry; D020007:Implants, Experimental; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D015415:Biomarkers; D004343:Drug Implants; D005353:Fibronectins; D009414:Nerve Growth Factors