Abstract
One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.
Similar content being viewed by others
References
Awaya A, Kobayashi H, Horikomi K, Tanaka S, Kabir AM, Yokoyama K, Ohno H, Kato K, Kitahara T, Tomino I, Isayama S, Nakamura S (1993) Neurotropic pyrimidine heterocyclic compounds. I. The newly synthesized pyrimidine compounds promote neurite outgrowth of GOTO and neuro 2a neuroblastoma cell lines, and potentiate nerve growth factor (NGF)-induced neurite sprouting of PC 12 cells. Biol Pharm Bull 16: 248–253
Bijlsma WA, Jennekens FGI, Schotman P, Gispen WH (1983) Stimulation by ACTH4–10 of nerve fiber regeneration following sciatic nerve crush. Muscle Nerve 6: 104–112
Derby A, Engleman VW, Frierdich GE, Neises G, Rapp SR, Roufa DG (1993) Nerve growth factor facilitates regeneration across nerve gaps: morphological and behavioral studies in rat sciatic nerve. Exp Neurol 119: 176–191
Gershenbaum MR, Roisen FJ (1980) The effects of dibutyryl cyclic adenosine monophosphate on the degeneration and regeneration of crush-lesioned rat sciatic nerves. Neuroscience 5: 1565–1580
Hanaoka Y, Ohi T, Furukawa S, Furukawa Y, Hayashi K, Matsukura S (1992) Effect of 4-methylcatechol on sciatic nerve growth factor level and motor conduction velocity in experimental diabetic neuropathic process in rats. Exp Neurol 115: 292–296
Horowitz SH (1989) Therapeutic strategies in promoting peripheral nerve regeneration. Muscle Nerve 12: 314–322
Koning PD, Brakkee JH, Gispen WH (1986) Methods for producing a reproducible crush in the sciatic and tibial nerve of the rat and rapid and precise testing of return of sensory function. Beneficial effects of melanocortins. J Neurol Sci 74: 237–246
Lundborg G (1988) Nerve regeneration. In: Nerve injury and repair. Churchill Livingstone, Edinburgh, pp 149–195
Martenson C, Stone K, Reedy M, Sheetz M (1993) Fast axonal transport is required for growth cone advance. Nature 355: 66–69
Matthews MA (1968) An electron microscopic study of the relationship between axon diameter and initiation of myelin production in the peripheral nervous system. Anat Rec 161: 337–352
McQuarrie IG (1989) Axonal transport and the regenerating nerve. In: Seil FJ (ed) Neural degeneration and transplantation. Liss, New York, pp 29–42
Raivich G, Kreutzberg GW (1993) Peripheral nerve regeneration: role of growth factors and their receptors. Int J Dev Neurosci 11: 311–324
SAS Institute (1988) SAS/STAT User's Guide, Release 6.03. SAS Institute, Cary, NC
Tanaka K, Webster H deF (1991) Myelinated fiber regeneration after crush injury is retarded in sciatic nerves of aging mice. J Comp Neurol 308: 180–187
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jiang, X.M., Ohnishi, A., Yamamoto, T. et al. The effect of MS-818, a pyrimidine compound, on the regeneration of peripheral nerve fibers of mice after a crush injury. Acta Neuropathol 90, 130–134 (1995). https://doi.org/10.1007/BF00294311
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00294311