Effects of axonal injury on ganglion cell survival and glutamate homeostasis

Abstract

Axonal trauma leads to a series of pathologic events that can culminate in neuronal death. Optic nerve crush can be used to explore histologic and molecular changes in traumatic central nervous system malfunction. Although the precise mechanisms of retinal ganglion cell death after optic nerve crush have not been elucidated, glutamate antagonists can protect retinal ganglion cells after axotomy. We, therefore, evaluated the effect of optic nerve crush on levels of extracellular glutamate. Ganglion cell survival and extracellular glutamate levels were assessed from 1 to 28 days after optic nerve crush in Long-Evans rats. Optic nerve crush led to a rise in extracellular glutamate; this rise was blocked by treatment with memantine, riluzole, and nimodipine. Partial optic nerve crush leads to an increase in vitreal glutamate, perhaps through release of intracellular contents. This released glutamate can contribute to additional ganglion cell loss. Future work will help to additionally unravel the steps by which axotomy induces excitotoxic damage to ganglion cells, and perhaps indicate protective interventions.