There are phenotypic and functional differences between vascular endothelium from different tissues and between microvascular and macrovascular endothelial cells (ECs) from the same tissue. Relatively little is known about the human blood-nerve barrier (BNB). We report the development of an in vitro BNB model using primary human endoneurial ECs freshly isolated and purified from decedent sciatic nerves via endoneurial stripping, connective tissue enzymatic digestion, and density centrifugation. Primary human endoneurial ECs are spindle shaped and contact inhibited. They rapidly differentiate to form capillary-like networks and microvessels, bind Ulex Europaeus Agglutinin 1 lectin, express von Willebrand factor, and endocytose acetylated low-density lipoprotein. They also express specific transport and cellular adhesion molecules and tight junction proteins, consistent with cells that form a highly restrictive endothelial barrier similar to the blood-brain barrier. When cultured on collagen-coated transwell inserts, the primary human endoneurial ECs develop an in vitro BNB with high transendothelial electrical resistances (160 Omega x cm(2); maximal 12 days after seeding) and low solute permeability coefficient to fluoresceinated high-molecular weight (70 kDa) dextran (2.75 x 10(-3) cm/minute). This in vitro BNB model retains essential known or expected characteristics of the human BNB and has many potential applications for studies of solute, macromolecule, microbial, virus, and leukocyte interactions with this highly specialized endothelial barrier.

No abstract

This study suggests that CCL2 expressed by Schwann cells and CXCL10 expressed by endoneurial endothelial cells may induce F4/80+ macrophage and CD3+ T cell-mediated inflammation and demyelination in sm-EAN. CCL2-CCR2 and CXCL10-CXCR3 signalling pathways are potential targets for therapeutic intervention in peripheral nerve inflammation.

The objective of this study was to define the behavioral, electrophysiological, and morphological characteristics of spontaneous autoimmune peripheral polyneuropathy (SAPP) in female B7-2 deficient non-obese diabetic (NOD) mice. A cohort of 77 female B7-2 deficient and 31 wild-type control NOD mice were studied from 18 to 40 weeks of age. At pre-defined time points, the dorsal caudal tail and sciatic motor nerve conduction studies (MNCS) were performed. Sciatic nerves were harvested for morphological evaluation. SAPP mice showed slowly progressive severe weakness in hind and forelimbs without significant recovery after 30 weeks of age. MNCS showed progressive reduction in mean compound motor action potential amplitudes and conduction velocities, and increase in mean total waveform duration from 24 to 27 weeks of age, peaking between 32 and 35 weeks of age. Toluidine blue-stained, semi-thin plastic-embedded sections demonstrated focal demyelination associated with mononuclear cell infiltration early in the disease course, with progressively diffuse demyelination and axonal loss associated with more intense mononuclear infiltration at peak severity. Immunohistochemistry confirmed macrophage-predominant inflammation. This study verifies SAPP as a progressive, unremitting chronic inflammatory demyelinating polyneuropathy with axonal loss.

Mice provide an important tool to investigate human neuromuscular disorders. The variability of electrophysiological techniques limits direct comparison between studies. The purpose of this study was to establish normative motor nerve conduction data in adult mice. The dorsal caudal tail nerve and sciatic nerve motor conduction studies were performed bilaterally on restrained anesthetized adult mice. The means and standard deviations for each electrophysiological parameter were determined in normal mice. Data were compared with inflammatory demyelinating polyneuropathy mice to determine whether these parameters discriminate between normal and abnormal peripheral nerves. Normal adult mice had a distal latency of 0.89 (+/-0.17) ms and 0.75 (+/-0.09) ms, distal compound motor unit action potential amplitude of 13.2 (+/-5.9) mV and 28.1 (+/-8.3) mV, and conduction velocity of 74.6 (+/-9.0) m/s and 76.5 (+/-8.3) m/s, respectively. These data were validated by the finding of statistically significant differences in several electrophysiological parameters that compared normal and polyneuropathy-affected mice. A standardized method for motor nerve conduction studies and associated normative data in mice should facilitate comparisons of disease severity and response to treatment between studies that use similar models. This would assist in the process of translational therapeutic drug design in neuromuscular disorders.