Physiological changes in the sciatic nerve endoneurium of lead-intoxicated rats: a model of endoneurial homeostasis

Ananda Weerasuriya, Geoffry L. Curran, Joseph F. Poduslo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The effects of inorganic lead (Pb) on peripheral nerves were studied by measuring the permeability coefficient-surface area product to albumin (PSA) of the blood-nerve interface (BNI), water and Pb content of endoneurium, and residual endoneurial plasma volume (Vp) of sciatic nerves of adult rats maintained on a 4% Pb diet for 2-12 weeks. Additionally, body weight, haematocrit, and blood Pb levels were also monitored. Within 1 week, both blood and endoneurial Pb levels had increased significantly above background levels and continued to increase up to the 6th week. Thereafter, over the next 6 weeks, the blood Pb levels were relatively stable, while the endoneurial Pb levels decreased sharply to a quarter of their peak values. The wet/dry weight ratio of the endoneurium, an indicator of nerve oedema, increased by about 30% from the 4th to 12th week, reaching a water content of 75% corresponding to a 24% increase of the total fascicular area. PSA increased only by the 8th week, without an accompanying increase in Vp. This suggests that the increase in PSA reflects an increase in the permeability of the BNI. Furthermore, the moderate 3-fold increase in PSinA is more consistent with an adaptive response of the BNI to changes in the endoneurial microenvironment rather than a massive breakdown or disruption of the BNI. This is supported by the inconsistent or mild leakage of horseradish peroxidase from endoneurial capillaries observed in Pb-intoxicated rats5,19. The present study quantitatively confirms the prevalent hypothesis on the pathogenetic mechanism of Pb neuropathy that Pb accumulation in Schwann cells and myelin causes a primary segmental demyelination and nerve oedema, followed by an epiphenomenal increase in BNI permeability. This hypothesis is further elaborated to postulate that the increase in permeability of the BNI is a dynamic, adaptive response to maintain the relative constancy of the milieu interieur of axons and Schwann cells.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalBrain Research
Issue number1-2
StatePublished - May 28 1990


  • Albumin
  • Blood-nerve interface
  • Endoneurial capillary
  • Endoneurium
  • Lead neuropathy
  • Peripheral nerve
  • Permeability
  • Sciatic nerve

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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