Macrophage colony stimulating factor (M-CSF) protects spiral ganglion neurons following auditory nerve injury: morphological and functional evidence

Because hearing disturbance due to auditory nerve dysfunction imposes a formidable burden on human beings, intense efforts have been expended in experimental and clinical studies to discover ways to restore normal hearing. However, the great majority of these investigations have focused on the peripheral process side of bipolar auditory neurons, and very few trials have focused on ways to halt degenerative processes in auditory neurons from the central process side (in the cerebellopontine angle). In the present study, we investigated whether administration of macrophage colony-stimulating factor (M-CSF) could protect auditory neurons in a rat model of nerve injury. The electrophysiological and morphological results of our study indicated that M-CSF could ameliorate both anterograde (Wallerian) and retrograde degeneration in both the CNS and PNS portions of the auditory nerve. We attribute the success of M-CSF therapy to the reported functional dichotomy (having the potential to cause both neuroprotective and neurotoxic effects) of microglia and macrophages. Whether the activities of microglia/macrophages are neuroprotective or neurotoxic may depend upon the nature of the stimulus that activates the cells. In the present study, the neuroprotective effects of M-CSF that were observed could have been due to M-CSF we administered and to M-CSF released from endothelial cells, resident cells of the CNS parenchyma, or infiltrating macrophages. Another possibility is that M-CSF ameliorated apoptotic auditory neuronal death, although this hypothesis remains to be proved in future studies.