Present address: Dept of Animal Physiology, Biology, Ruhr University Bochum, D44780 Bochum, Germany.
Inhibition of collagen IV deposition promotes regeneration of injured CNS axons
Article first published online: 27 AUG 2008
European Journal of Neuroscience
Volume 11, Issue 2, pages 632–646, February 1999
How to Cite
Stichel, C. C., Hermanns, S., Luhmann, H. J., Lausberg, F., Niermann, H., D'Urso, D., Servos, G., Hartwig, H.-G. and Müller, H. W. (1999), Inhibition of collagen IV deposition promotes regeneration of injured CNS axons. European Journal of Neuroscience, 11: 632–646. doi: 10.1046/j.1460-9568.1999.00466.x
- Issue published online: 27 AUG 2008
- Article first published online: 27 AUG 2008
- Received 1 April 1998, revised 22 September 1998, accepted 28 September 1998
- axonal regeneration;
- basal membrane;
- growth barrier;
Scarring impedes axon regrowth across the lesion site and is one major extrinsic constraint to effective regeneration in the adult mammalian central nervous system. In the present study we determined whether specific biochemical or immunochemical modulation of one major component of the scar, the basal membrane (BM), would provide a means to stimulate axon regeneration in the mechanically transected postcommissural fornix of the adult rat. Basal membrane developed within the first 2 weeks after transection in spatiotemporal coincidence with the abrupt growth arrest of spontaneously regrowing axons. Local injection of anticollagen IV antibodies or α, α′-dipyridyl, an inhibitor of collagen triple helix formation and synthesis, significantly reduced lesion-induced BM deposition. This treatment allowed massive axon elongation across the lesion site. Anterograde tracing provided unequivocal evidence that regenerating axons follow their original pathway, reinnervate the appropriate target, the mammillary body, and become remyelinated with compact myelin. Presynaptic electrophysiological recordings of regenerated fibre tracts showed recovery to nearly normal conduction properties. Our results indicate that lesion-induced BM is an impediment for successful axonal regeneration and its reduction is a prerequisite and sufficient condition for regrowing axons to cross the lesion site.