Date of Award

1992

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

After years of investigation into blood-nervous tissue barriers controversies remain regarding the permeability of blood vessels to macromolecules in the enteric nervous system, the endoneurium of peripheral nerve, and the spaces between satellite cells and neurons in sensory and sympathetic ganglia.;The permeability of the above areas of the peripheral nervous system was investigated in rats using the following intravenously administered tracers: rhodamine-labelled bovine albumin; horseradish peroxidase; acriflavine and ethidium. The last two, which are fluorescent cationic dyes were shown to bind to serum proteins. In addition immunohistochemical staining for endogenous albumin was performed. One long-term study was done in which rhodamine-labelled bovine albumin was injected subcutaneously, once daily, for one week. With all these methods, it was possible to show that blood vessels in the brain were impermeable, whereas those in circumventricular organs were permeable, thus validating their application to regions in which the existence of permeable vessels was questionable.;Rhodamine-labelled bovine albumin was seen in all the extracellular spaces in sympathetic and sensory ganglia, even after short times in the circulation. The endoneurium of peripheral nerve contained this tracer only in rats in which it had been injected daily for one week. At no time did this fluorescent albumin enter the enteric ganglia. Positive immunohistochemical staining for endogenous albumin was present in the enteric nervous system, in the endoneurium of peripheral nerve, in the spaces between satellite cells and neurons in sensory ganglia, and around neurons in sympathetic ganglia. Horseradish peroxidase, which is present in the blood for about 5 minutes following intravenous injection, penetrated the enteric nervous system, and the extracellular spaces between satellite cells and neurons in sensory ganglia, but it did not enter the endoneurium of peripheral nerve. The fluorochromes acriflavine and ethidium entered enteric, sympathetic and sensory ganglia, but not the endoneurium of peripheral nerve.;In conclusion, the enteric nervous system, sympathetic and sensory ganglia are permeable to most circulating macromolecules. The endoneurium of peripheral nerve is permeable only to macromolecules that are present in the circulation for at least one week, so the transudation or diffusion in this tissue must occur more slowly than elsewhere. These permeabilities may explain how some pathogens enter the nervous system.

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