Assessment of the nerve microenvironment in experimental lead neuropathy permits an evaluation of the role that blood-nerve barrier disruption plays in the development of segmental demyelination observed during chronic lead intoxication. Endoneurial fractions from the sciatic nerves of 60-day-old rats maintained on 4% lead carbonate for 3 to 24 weeks and their corresponding pair-fed controls were evaluated for protein and hydroxyproline distribution as well as for protein compositional changes determined by sodium dodecyl sulfate-pore gradient electrophoresis (SDS-PGE). A redistribution of both protein and hydroxyproline was observed in the endoneurial fractions, and SDS-PGE analysis revealed both qualitative and quantitative differences in a large number of proteins. In particular, the endoneurial albumin concentration began to increase after 6 weeks of the lead diet and reached a level at 24 weeks that was twice that of the pair-fed control. To demonstrate that this change in endoneurial albumin concentration resulted from a breakdown of the blood-nerve barrier and was not due to an accumulation of albumin, 125I-albumin was injected intravenously into rats maintained on a lead diet for different times. After waiting 48 hr to allow equilibration of the labeled albumin in all body fluids, the specific activities for both serum and an endoneurial supernatant fraction containing the albumin were compared to pair-fed controls. The ratios of specific activity in lead-fed rats to controls showed a 1.3-fold increase at 6 weeks which increased by 3.9-fold at 12 weeks. These changes in the endoneurial albumin concentration, therefore, reflect an alteration in the blood-nerve barrier which commences 6 weeks after the lead treatment. Since lead reaches a maximum in the endoneurium at 5 weeks, these changes in the barrier probably are unrelated to the direct toxic effect of lead on Schwann cells and the subsequent onset of segmental demyelination. Furthermore, it is suggested that blood-nerve barrier breakdown in human peripheral neuropathies can be evaluated by determining a serum/endoneurial albumin concentration ratio using biopsied, neuropathic, human sural nerve.
|Original language||English (US)|
|Number of pages||8|
|State||Published - 1982|
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