Effect on the rat hypoglossal nucleus of vinblastine and colchicine applied to the intact or transected hypoglossal nerve

Abstract

The possibility that interruption of axonal transport in otherwise intact axons induces retrograde neuronal and nonneuronal reactions was examined. In addition, the proposal that blockade of axonal transport proximal to nerve injury might inhibit or delay the axon reaction was examined. Cuffs containing various doses of vinblastine were applied to the intact hypoglossal nerve. Colchicine was applied in a similar way to the intact hypoglossal nerve, injected directly into the intact nerve, or administered proximal to the site of hypoglossal nerve transection. The effect on retrograde axonal transport in the nerve was evaluated in the vinblastine experiments by the retrograde horseradish peroxidase (HRP) technique following injection of HRP or wheat germ agglutinin-conjugated HRP into the tongue. A dose of 0.01% caused an almost complete, but transient, blockade of the retrograde transport of the tracer, and induced a clearcut chromatolytic reaction in hypoglossal neurons. The chromatolytic changes were accompanied by a significant increase in the number of glial cells, many of which were identified as microglia. Similar results were obtained with colchicine alone or in combination with nerve transection. Signs of Wallerian degeneration after vinblastine treatment (0.01%) were observed only in a small number of myelinated fibers. The findings are compatible with the view that depletion of retrogradely transported factors from the peripheral innervation territory (including the distal nerve stump) to the perikaryon and/or a premature return of anterogradely transported substances at the site of drug exposure are factors inducing retrograde neuronal and nonneuronal changes.