Glycosaminoglycans treatment increases IGF-I muscle levels and counteractsmotor neuron death: A novel nonanticoagulant action

The present study shows that sciatic nerve crush in 2-day-old rats causes e xtensor digitorum longus (EDL) muscle atrophy and motor neuron loss and tha t treatment with glycosaminoglycans (GAGs) promotes muscle reinnervation, m otor neuron survival, and markedly increases insulinlike growth factor-I (I GF-I) content in the denervated muscles, EDL muscle denervation-induced atr ophy in saline-treated rats is progressive and reaches the greatest extent at 42 days after birth, which correlates with reduced EDL weight growth. Th ere is also a partial reinnervation as shown by the number of reinnervated EDL muscle fibers (65.4% of control) and by the poor restoration of the ind irect isometric twitch tension (62% of control) that is further reduced und er tetanic stimulation (34% of control). The number of surviving motor neur ons that innervate EDL muscle drops from 55 +/- 3 to 29 +/-. 8, In GAGs-tre ated 42-day-old rats, the effects of neonatal nerve lesioning on EDL muscle atrophy and denervation are successfully reversed, and the isometric twitc h tension and the capacity to hold tetanic stimulation are restored to almo st control levels, The number of surviving EDL motor neurons is also increa sed to 43 +/- 4. Treatment with GAGs selectively affects IGF-I content in d enervated hindlimb muscles, which is augmented from 7.02 +/- 0.71 ng/mg tis sue to 25.72 +/- 0.7 in the EDL and from 3.2 +/- 0.18 to a robust 211 +/- 9 .6 in the soleus, J, Neurosci, Res. 55:496-503, 1999. (C) 1999 WiIey-Liss, Inc.