First place--Resident Basic Science Award 1990. Fibronectin-laminin combination enhances peripheral nerve regeneration across long gaps.
An exogenous fibronectin-laminin (FN-LAM) solution was added into silicone chambers to determine the effects on peripheral nerve regeneration across 18-mm long gaps. The sciatic nerves of adult rats were sutured into silicone chambers 20 mm in length, creating an 18-mm gap between the proximal and distal nerve stumps. The chambers were filled with either a mixture of fibronectin and laminin (500 micrograms/ml each) or a solution of cytochrome C (1 mg/ml) as the control. After six weeks, the animals were killed and the chambers were examined for regeneration. Seventy percent of the animals from the FN-LAM group demonstrated regeneration across the 18-mm gaps, compared to only 30% in the control group. The combination of FN-LAM significantly increased the number of axons that grew into the distal end of the chamber (FN-LAM, 1325 +/- 522; cytochrome C, 153 +/- 104; p = 0.03). Examination of the distal tributaries of the sciatic nerve revealed axons only in the FN-LAM group; none were found in the control group. Quantitative analysis of neurons, retrogradely labeled with horseradish peroxidase via injection of the sciatic nerve distal to the regenerated segment, revealed a greater number of sensory and motor neurons in the FN-LAM group compared to the control group. Morphometric studies revealed that the mean area of the regenerated segment in the FN-LAM group was 37% larger than the controls, and ultrastructural analysis demonstrated a more mature regenerated nerve. This is the first in vivo demonstration that this combination of fibronectin and laminin significantly enhances the regeneration of myelinated axons across a long nerve gap in the rat sciatic nerve.
Woolley
A L
AL
Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110.
Hollowell
J P
JP
Rich
K M
KM
D000047:Academies and Institutes; D000818:Animals; D001363:Awards and Prizes; D001369:Axons / Q000187:drug effects; D003574:Cytochrome c Group / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000494:pharmacology*; D007797:Laminin / Q000494:pharmacology*; D009186:Myelin Sheath / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009493:Neurosurgery; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects; D014481:United States
D003574:Cytochrome c Group; D005353:Fibronectins; D007797:Laminin