Studies on the degenerative and regenerative phenomena occurring after transection and repair of the sciatic nerve in rats: effects of acetyl-L-carnitine.
The effects of acetyl-L-carnitine on some degenerative and regenerative phenomena following sciatic nerve transection in rats, were studied. In Experiment 1, acetyl-L-carnitine was administered intraperitoneally at the dose of 50 mg/kg/day for 28 and 56 days following transection and microsurgical repair of the sciatic nerve. On day 56, the acetyl-L-carnitine-treated rats showed a significantly (p less than 0.05) better motor recovery ("clinical assessment") of the peroneal component of the sciatic nerve than the control rats. Twenty-eight days after nerve repair, the acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of myelinated axons in the postlesional nerve stump than control rats. Finally, the treated rats had a significantly lower (p less than 0.05) presence of atrophic fibres in the extensor digitorum longus muscle. In Experiment 2 the sciatic nerve was cut. To prevent spontaneous regeneration, a metallic clip was applied to the distal nerve stump and then the nerve stumps were positioned in different anatomical compartments. After surgery, a group of rats was treated with acetyl-L-carnitine dissolved in the drinking water (75 mg/kg/day). Another group of rats received normal water and served as the control group. Three, 6, 9, 12 and 18 months postoperatively, in the rats of both groups, the proximal sciatic nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. While in untreated rats the number of horseradish peroxidase-labelled neurons decreased with the increase in denervation time, in acetyl-L-carnitine-treated rats the number of horseradish peroxidase-labelled neurons remained stable for as long as 12 months of denervation and decreased only after 18 months of denervation. Furthermore, acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of horseradish peroxidase-labelled neurons with respect to untreated rats both after 9 and 12 months of denervation. In Experiment 3, the sciatic nerve was cut and then repaired after periods of 3, 6, 9, 12, and 18 months. Four months after nerve repair, the sciatic nerve was again cut and the proximal nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. Both acetyl-L-carnitine-treated and untreated rats showed a tendency to have an increased number of horseradish peroxidase-labelled neurons with respect to intact rats of correspondent ages.(ABSTRACT TRUNCATED AT 400 WORDS)
Fernandez
E
E
Institute of Neurosurgery, Catholic University School of Medicine, Rome, Italy.
Pallini
R
R
Gangitano
C
C
Del Fa
A
A
Olivieri-Sangiacomo
C
C
Sbriccoli
A
A
Ricoy
J
J
Rossi
G F
GF
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives*; D006735:Horseradish Peroxidase; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009410:Nerve Degeneration / Q000187:drug effects*; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
D000108:Acetylcarnitine; D006735:Horseradish Peroxidase; D002331:Carnitine