title: Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy.
abstract: Onset and nature of ultrastructural changes in endoneurial vasa nervorum during the pathogenesis of leprosy neuropathy and possibly associated alterations in the "blood-nerve barrier" were investigated, together with perineurial barrier functioning, in mice infected 20-28 months previously with Mycobacterium leprae and in (ageing) non-infected mice. Barriers were tested by i.v. administration of markers (Trypan blue and ferritin) 1-4 days before killing the mice. Twenty-eight months after infection, histopathology of sciatic nerves was comparable to that seen in sensory nerves in clinically early human (borderline-) lepromatous leprosy. Schwann cells and endoneurial macrophages were bacillated, endothelia of endoneurial vessels not, and the perineurium rarely. Many infected mice and all (ageing) controls possessed ultrastructurally and functionally normal endoneurial vessels. Their continuous endothelium with close junctions had prevented marker passage, even when surrounding endoneurial tissue cells were quite heavily bacillated. The perineurium was also normal. By contrast, in infected mice showing hind limb paralysis serious histopathologic involvement and large globi of bacilli intrafascicularly in sciatic nerves, endoneurial blood vessels were abnormal. Open endothelial junctions, extreme attenuation, fenestrations, and luminal protrusions were all features comparable to neural microangiopathy encountered in leprosy patients (Boddingius 1977a, b). The "blood-nerve barrier" clearly had become defective allowing excessive exudation of Trypan blue and ferritin, via four pathways from the vessel lumen, deep into surrounding endoneurial tissues but halted by a normal perineurial barrier. Markers in such "blue" nerves were not found in bacillated or non-bacillated Schwann cells, thus denying significant phagocytotic and lysosomal activities of Schwann cells at this stage of neuropathy. Possible implications of barrier performances for anti-leprosy drug treatment of patients are discussed.
mesh_terms: D000367:Age Factors; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D005260:Female; D007918:Leprosy / Q000473:pathology*; D051379:Mice; D008808:Mice, Inbred CBA; D008854:Microscopy, Electron; D010525:Peripheral Nerves / Q000473:pathology* / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000473:pathology*; D012583:Schwann Cells / Q000473:pathology; D014650:Vasa Nervorum / Q000473:pathology* / Q000648:ultrastructure