The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

Objectives: Paraplegia following spinal cord ischaemia represents the most severe complication of aortic surgery. Shock wave treatment (SWT) was shown to induce angiogenesis and regeneration in ischaemic tissue. In pre-clinical as well as clinical studies SWT had a favourable effect on ischaemic myocardium. We therefore hypothesised that SWT may have a beneficial effect on spinal cord ischaemia as well. Methods: Aortic cross clamp was performed between left carotid and subclavian artery in 10–12-week-old male C57/Bl6 mice. Animals were randomly divided to treatment group (SWT, 500 impulses at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 6. RNA expression of angiogenic and inflammatory cytokines was measured after 24 and 48 h. Immunofluorescence staining for degenerating neurons (Fluoro Jade B) and macrophages (Iba-1) was performed after 7 days. Results: Real-time PCR analysis revealed higher gene expression of angiogenic factors, vascular endothelial growth factor-A (VEGF-A) after 24 h (SWT 0.21 ± 0.06 vs CTR 0.07 ± 0.01, P = 0.028) and 48 h (SWT 0.11 ± 0.02 vs CTR 0.07 ± 0.01, P > 0.05) as well as hypoxia inducible factor-1α (HIF-1α) after 24 h (SWT 0.11 ± 0.04 vs CTR 0.04 ± 0.01, P > 0.05) and 48 h (SWT 0.09 ± 0.02 vs CTR 0.01 ± 0, P = 0.016). Early increase of inflammatory mRNA expression was observed after 24 h by TNF-α (SWT 0.03 ± 0.003 vs CTR 0.005 ± 0.003, P = 0.007) and TGF-β (SWT 0.57 ± 0.05 vs CTR 0.17 ± 0.08, P = 0.003). This resulted in a markedly decreased number of degenerating neurons in the treatment group 7 days after ischaemia (SWT 74.50 ± 8.14 vs CTR 250.2 ± 42.98, P = 0.0025). Conclusion: Shock wave treatment results in a marked decrease of degenerating neurons and may therefore develop as an adjunct to the treatment armamentarium for paraplegia upon aortic cross clamp.