Comparison of fluctuating and sustained neural pressure perturbations on axonal transport processes in the optic nerve

Abstract

Pressure changes within the central nervous system (CNS) have the capacity to provoke neurodegeneration by perturbing axonal homeostatic processes. The pathogenic role of axonal transport dysfunction in diseases characterised by sustained pressure elevation have been clearly delineated, however the patho-physiogical mechanisms underlying neurological disorders typified by measurable fluctuations in CNS pressure remains unclarified. This study utilises the rabbit optic nerve, a myelinated, mammalian neuronal tract to compare the effects of sustained pressure elevation and fluctuating pressure change on axonal transport processes. In 5 rabbits, neural pressure was sustained at 10 mm Hg and 40 mm Hg in the right and left optic nerves, respectively, for 6 hours. In another 5 rabbits, neural pressure was modulated between 7.5 mm Hg and 57.5 mm Hg at 30 minute intervals in the right optic nerve, and sustained at 40 mm Hg in the left optic nerve for 6 hours. Rhodamine-β-isothiocyanate, an axonal transport tracer, was used to quantify axonal transport differences between normal-, high- and fluctuating-pressure nerves. Axonal transport rates in high-pressure nerves were significantly lower than normal-pressure nerves. The effects of fluctuating-pressure and sustained high-pressure on axonal transport processes were not significantly different. The findings of this study suggest that the magnitude of pressure elevation and the profile of pressure change over time is important in modulating axonal function. It also implicates the importance of axonal transport dysfunction in the process of neurodegeneration. These results may have relevance for understanding patho-physiological mechanisms involved in pseudotumor cerebri, syringomyelia, hydrocephalus and glaucoma—diseases characterised by fluctuating pressure changes.