Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors.
Injury to the sciatic nerve leads to the transganglionic degeneration of sensory axons and to the induction of neurotrophins and p75 nerve growth factor receptor synthesis by the denervated Schwann cells. Sciatic nerve axotomy caused a marked loss of substance P and of met-enkephalin in the lumbar cord. Substance P immunostaining and pre-proenkephalin mRNA expression were reduced in the dorsal horn layers I and II ipsilaterally to the lesion. Treating rats with low doses (0.25 mg/kg) of heparin or COS 8, a natural glycosaminoglycan mixture with low anticoagulant activity, the peptide loss was prevented and the content increased of about 50% above control values. The effects of COS 8 treatment were also evident on Schwann cells. COS 8 augmented the increase of nerve growth factor, brain-derived neurotrophic factor, and NT-3 mRNA expression in the distal stump of the axotomized sciatic nerve. Therefore, it can be concluded that glycosaminoglycans neuroprotective effects on lesioned sensory axons might have been mediated by the dramatic promotion of neurotrophin synthesis. Although the in vitro studies (Lesma et al.: J Neurosci Res, 1996) suggested also a likely direct effect as extracellular matrix components that is not mediated by trophic factors.
Gorio
A
A
Laboratory for Research on Pharmacology of Neurodegenerative Disorders, Dept. Medical Pharmacology, Milano, Italy.
Vergani
L
L
Ferro
L
L
Prino
G
G
Di Giulio
A M
AM
D000818:Animals; D001369:Axons / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion; D003714:Denervation; D004744:Enkephalin, Methionine / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D012583:Schwann Cells / Q000187:drug effects; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D013373:Substance P / Q000096:biosynthesis / Q000235:genetics; D014855:Wallerian Degeneration / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; C105070:COS 8 preparation; D006025:Glycosaminoglycans; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D013373:Substance P; D004744:Enkephalin, Methionine; D006493:Heparin