Macrophage invasion into injured cochlear nerve and its modification by methylprednisolone

Post-traumatic invasion of macrophages into the cochlear nerve of the rat and measurement of how their invasion was modified by the administration of methylprednisolone were investigated for the first time by using a reproducible and quantifiable experimental model of cochlear nerve injury. Two weeks after precise cochlear nerve compression, a massive invasion of ED1 immunostained macrophages was observed at the compressed portion of the cochlear nerve, and this invasion of macrophages was markedly reduced in the rats to which methylprednisolone had been administered during the pre- and post-compression period. Concomitantly, the residual number of spiral ganglion cells was found to be greater in the compression+methylprednisolone group than in the control compression group. The tissue loss observed in the lesion epicenter was also significantly less in the compression+methylprednisolone group than in the control compression group. The results of our present study demonstrated the effectiveness of methylprednisolone treatment to ameliorate trauma induced cochlear nerve degeneration in the acute phase. However, these results may reflect the sum effects of methylprednisolone on macrophages, including both its beneficial effect by inhibiting the negative aspects of macrophages through attenuating macrophage recruitment to the lesion site, and at the same time an undesirable effect by sacrificing the positive aspects of macrophage function. Moreover, one reservation should be added that the protective effects of steroid to injured cochlear nerve may have operated via a pathway not related to macrophage function. Besides macrophages, various cells and factors participate in the process of CNS injury, and their effects may potentially work either positively or negatively with respect to CNS protection and regeneration at each particular time during the on-going process of CNS injury. Therefore, future investigation in CNS injury should be directed toward understanding such complex mechanisms involved in this process.