POLYAMINES INCREASE IN THE BRAIN-STEM AND CEREBELLUM FOLLOWING LABYRINTHECTOMY

The goal of this investigation was to test the hypothesis that unilate ral damage to the vestibular end-organ (labyrinthectomy) stimulates po lyamine synthesis in central vestibular neural structures that mediate the process of behavioral recovery (vestibular compensation). Pharmac ological studies have shown that compensation can be altered by oc-dif luoromethylornithine (DFMO), a specific inhibitor of polyamine synthes is. Because polyamines are important in regeneration, development and modulation of N-methyl-D-aspartate (NMDA) excitatory amino acid recept ors, which mediate vestibular synaptic plasticity, we investigated cha nges in polyamines in specific central vestibular structures after uni lateral labyrinthectomy. The supernatant fraction of brain tissue homo genates was reacted with dansyl chloride. Dansylated polyamine derivat ives were quantified in the vestibular nuclei, cerebellum, and inferio r olive in both the control and the unilaterally labyrinthectomized gu inea pig by high-performance liquid chromatography-fluorometric detect ion. No left-right differences in putrescine, spermidine, or spermine were detected in any brain parenchyma of controls. Polyamine imbalance , characterized by increased spermidine in the ipsilateral medial and lateral vestibular nuclei, was noted 12 and 24 h after unilateral laby rinthectomy (UL). In contrast, spermidine, spermine, and putrescine we re elevated bilaterally in the cerebellum and inferior olive after UL. These biochemical changes may represent neuronal modifications to est ablish a balance between the vestibular nuclei after unilateral labyri nthectomy. Elucidation of the role of polyamines in central vestibular function and in vestibular compensation offers promise for the develo pment of novel therapeutic strategies for treatment of vestibular diso rders.