A freeze-fracture study of the perineurium in galactose neuropathy: morphological changes associated with endoneurial...

Feeding rats with galactose as 40% of their diet results in peripheral nerve oedema related to the intrafascicular accumulation of galactitol and sodium. In this study, associated changes in the perineurium were examined by the freeze-fracture replication technique. Perineurial cells are linked by tight junctions (zonulae occludentes). In normal animals these are made up of anastomosing strands organized in a belt-like arrangement along the margins of continuous cells. The majority of the tight junctions in the galactose-fed animals displayed structural abnormalities. These ranged from slight separation of the strands to fragmentation and dispersal, with looping of isolated strands. Some of the tight junctions contained large dilated compartments within the junctional network. Short lengths of intramembranous particles, probably representing assembly or disassembly of tight junctional strands, were also observed. The membranes of perineurial cells normally possess numerous openings of caveolae. A quantitative assessment showed that the mean density of these caveolae openings was increased in the galactose-fed rats as compared with controls. The alterations in the tight junctions resemble those that have been produced experimentally in epithelia by subjecting them to abnormal osmotic gradients. They also resemble those seen in human diabetic neuropathy in which osmotic disturbances involving the perineurium have been considered to occur. If the alterations involve the inner layers of the perineurium, they are likely to impair its barrier function. The increased number of caveolae openings in galactose neuropathy may represent a reaction to the endoneurial oedema and indicate that the pinocytotic-like vesicles have a transport function.