Freeze-fracture observations on normal and abnormal human perineurial tight junctions: alterations in diabetic polyneuropathy

Abstract

Perineurial cells in the human sural nerve possess tight junctions which in freeze-fracture replicas are seen to be composed of networks of branching and anastomosing P face strands and E face grooves. Isolated circular tight junctions (maculae occludentes) may represent attachment devices between adjacent perineurial lamellae. At the overlapping margins of the cells, a belt-like tight junction (zonula occludens) encircles the cells and is believed to comprise a paracellular diffusion barrier. As the permeability of the perineurium has been found to be altered in diabetic polyneuropathy, the zonulae occludentes have been studied. In freeze-fracture replicas from cases of diabetic polyneuropathy a mixed population of structurally normal and abnormal junctions was observed. In some, the strands were abnormally curved with reduced numbers of intersections, the intervening plasma membrane displaying prominent P face concavities and E face convexities. At other sites, the junctions were severely disorganized and represented by fragmented and isolated strands with few intersections and numerous free ends. These abnormalities resemble changes that have been produced experimentally in epithelial tight junctions by osmotic damage. The possibility is considered that similar mechanisms could result in the alterations of the perineurial tight junctions in diabetic polyneuropathy and account for its impaired permeability barrier properties.

The Structural and Functional Integrity of Peripheral Nerves Depends on the Glial-Derived Signal Desert Hedgehog

“…At this point, we can only speculate. The breakdown of the tissue-nerve and blood-nerve barriers is likely to alter the chemical composition of the endoneurial space and therefore the microenvironment of the axon-Schwann cell units (Olsson, 1990;Beamish et al, 1991;Sinnreich et al, 2005). This, however, is unlikely to be the cause of the adverse changes in myelinating Schwann cells, the increase in SLI, because this is already evident at P10, which is before these barriers are effective (Kristensson and Olsson, 1971;Weerasuriya et al, 1990).…”

Localization in human diabetic peripheral nerve of N ε -carboxymethyllysine-protein adducts, an advanced glycation endproduct

“…It is of note that perineurial cells and their basement membranes as well as perineurial collagens reacted with AGE. Perineurial cells and their basement membranes are thought to play a crucial role in the maintenance of perifascicular diffusion barrier to the macromolecules such as AGE-modified proteins [33,34]. It may be possible that the excessive accumulation of AGE-modified adducts in the perineurium as well as endoneurial microvasculature alters the endoneurial microenvironment and microcirculation and thereby contributes to the development of peripheral neuropathy in diabetes.…”

Receptor for advanced glycation endproduct (RAGE)–mediated nuclear factor‐κB activation in vasculitic neuropathy

“…The role of the perineurium in normal nerve is not clear, but it seems to provide an important barrier function 7, 18, 35, 36, 46, 50. Activation of the CML–RAGE–NF‐κB–IL‐6 axis in perineurial cells provides a model to explain the break of this barrier, resulting in functional or structural disturbances of the endoneurial space and accelerating necrosis of nerve fibers that are affected by local ischemia in vasculitic neuropathies 22, 46…”