Biphasic cellular response to transection in the newt optic nerve: glial reactivity precedes axonal degeneration

Morphological interactions between axons and glia within the lesioned newt optic nerve were studied at time periods prior to the onset of Wallerian degeneration. Optic nerves were transected 0.5 mm from the eye, animals were killed at 5, 10, 20 and 30 min post-lesion, and the intracranial half of the tract was examined with light and electron microscopy. A sequence of structural changes was observed within the time interval 5-30 min post-lesion. Over the first 20 minutes these changes primarily involved the endogenous neuroglia; there was a displacement of glial nuclei from the center to the periphery of the nerve and an increase of 50-100% in glial cytoplasmic and nuclear area. Nuclei of reactive glia were euchromatic and surrounded by a high density of Golgi, vesicles, mitochondria and filaments, the last of which extended throughout the expanded glial processes. Optic axons appear intact at 20 min post-lesion except for some separation between the axolemma and myelin sheath in some of the myelinated fibres. By 30 min post-lesion both myelinated and non-myelinated fibres were found in various stages of lysis. Many of the expanded glial processes contained a population of vesicles aggregated adjacent to the glial plasmalemma. Profiles of infolded glial membranes suggested the opening of such vesicles into the extracellular space around degenerating axons. We conclude that, after optic nerve injury, there are very rapid reactive changes in glia and axons, with the changes in glia preceding the degenerative events in axons.