BACKGROUND Brain-derived neurotrophic factor (BDNF) is an important factor in the development and neuroprotection of afferent auditory pathways. In this study, we investigated the expression of BDNF in the afferent auditory pathway after cochlear implantation (CI), hypothesizing that electrical stimulation after CI stimulates BDNF expression in the afferent auditory pathway. METHODS Archival human temporal bones from eight patients with a history of CI and five patients with normal hearing (ages 65-93 years old) were studied. Temporal bone specimens were immunoreacted with rabbit polyclonal antibodies against BDNF and mouse monoclonal antibodies against pan-neurofilaments. In cases of unilateral CI, the BDNF expression was compared with the contralateral unimplanted ear and normal temporal bones without hearing loss. RESULTS BDNF immunoreactivity (IR) localized to the spiral ganglion neurons (SGNs) somata and the surrounding satellite cells. BDNF-IR in the spiral ganglia was similar in the apical, middle, and basal hook regions. Neurofilament IR localized to SGN nerve fibers in both implanted and unimplanted cochleae. BDNF-IR in the SGN and satellite cells was significantly increased in the implanted specimens compared with the unimplanted specimens (p < 0.05) and the normal hearing specimens (p < 0.05). BDNF-IR expression was similar in the unimplanted cochlea and in the normal cochlea. BDNF protein expression was increased despite complete loss of the organ of Corti hair cells and supporting cells. Even in the cases of CI with a 6-mm first-generation electrode, BDNF expression was upregulated throughout the cochlea. CONCLUSIONS BDNF expression in the SGN appears to be upregulated by the electrical stimulation from CI. This study provides evidence that the electrical stimulation from CI may stimulate the expression of BDNF, playing a neuroprotective role in the rehabilitation of hearing in the deafened ear.