Glycosaminoglycans in nerve injury .2. 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 off met-enkephalin in the lumbar cord, Substance P immunostaining and pre-proenkephalin mBNA expression were reduced in the dorsal born 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 ins 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 off neurotrophin synthesis, Although the ins 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. (C) 1996 Wiley-Liss, Inc.