Ultrastructural and ultracytochemical studies on the blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis.

Abstract

We induced chronic relapsing experimental allergic encephalomyelitis (EAE), and studied the ultrastructural and ultracytochemical changes of the blood-brain barrier (BBB) in the demyelinating lesions of various stages of EAE. In the chronic, inactive stage with gliosis and perivascular fibrosis, the basal lamina (BL) of the perivascular processes of astrocytes was formed only partially, and neural parenchyma was not fully separated from the perivascular mesenchymal tissues by the BL of astrocytic processes. Vascular permeability of the BBB was studied using exogenous horseradish peroxidase (HRP) as the tracer: HRP extravasation was marked during the stages of both active myelin breakdown and removal of debris, and was recognized even at the inactive stage, although the degree was reduced to a very low level. The functions of the endothelia, assessed by ouabain-sensitive, K+-dependent p-nitrophenylphosphatase activity, were impaired as EAE progressed. The decrease in HRP leakage at the inactive stage suggests the endothelial impairment of active transport of metabolites including HRP. Along with the development of inflammatory demyelination in EAE, the BBB in affected areas became more and more altered, and gradual morphological and functional impairment of the BBB developed.