Fig. 1.

Gene therapy with NGF prevents bone marrow neuropathy. Immunohistochemical studies were carried out to compare the nerve fibre density in the bone marrow of non-diabetic and type 1 diabetic mice. The latter were randomised to receive Ad.hNGF or Ad.βGal. (a–d) Representative micrographs and bar graphs showing the density of neuronal fibres expressing the pan-neuronal marker PGP9.5 (a, b) and nociceptive fibres positive for substance P (c, d) (scale bar, 20 μm). Arrows point to positive fibres. (e) Representative immunofluorescence microscopy images identify substance P-containing sensory terminals, which were often associated with CD31-positive vascular structures (arrows) (scale bar, 50 μm). (f, g) Representative micrographs and bar graphs showing the density of NGF-positive neuronal fibres in bone marrow (scale bar, 50 μm). n = 4 per group (b, d); n = 5 per group (g). Data are expressed as means ± SEM. ^*p < 0.05, ^**p < 0.01 and ^***p < 0.001 vs non-diabetic animals; ^†p < 0.05 and ^††p < 0.01 vs type 1 diabetic mice with Ad.βGal. ND, non-diabetic; SP, substance P; T1DM, type 1 diabetic