title: Charge-balanced biphasic electrical stimulation inhibits neurite extension of spiral ganglion neurons.
abstract: Intracochlear application of exogenous or transgenic neurotrophins, such as neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF), could promote the resprouting of spiral ganglion neuron (SGN) neurites in deafened animals. These resprouting neurites might reduce the gap between cochlear implant electrodes and their targeting SGNs, allowing for an improvement of spatial resolution of electrical stimulation. This study is to investigate the impact of electrical stimulation employed in CI on the extension of resprouting SGN neurites. We established an in vitro model including the devices delivering charge-balanced biphasic electrical stimulation, and spiral ganglion (SG) dissociated culture treated with BDNF and NT-3. After electrical stimulation with varying durations and intensities, we quantified neurite lengths and Schwann cell densities in SG cultures. Stimulations that were greater than 50μA or longer than 8h significantly decreased SG neurite length. Schwann cell density under 100μA electrical stimulation for 48h was significantly lower compared to that in non-stimulated group. These electrical stimulation-induced decreases of neurite extension and Schwann cell density were attenuated by various types of voltage-dependent calcium channel (VDCC) blockers, or completely prevented by their combination, cadmium or calcium-free medium. Our study suggested that charge-balanced biphasic electrical stimulation inhibited the extension of resprouting SGN neurites and decreased Schwann cell density in vitro. Calcium influx through multiple types of VDCCs was involved in the electrical stimulation-induced inhibition.
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China; Department of Otolaryngology, Zhongshan Hospital of Fudan University, Shanghai, China; NHFPC Key Laboratory of Hearing Medicine, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China; NHFPC Key Laboratory of Hearing Medicine, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China; NHFPC Key Laboratory of Hearing Medicine, Shanghai, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Neurobiology, Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lai
authors.affiliation: Central laboratory, Eye & ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China; NHFPC Key Laboratory of Hearing Medicine, Shanghai, China; Shanghai Hearing Medical Center, Shanghai, China. Electronic address: fjswzm2015@126.com.
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China; NHFPC Key Laboratory of Hearing Medicine, Shanghai, China; Shanghai Hearing Medical Center, Shanghai, China. Electronic address: lisf@fudan.edu.cn.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002452:Cell Count; D002478:Cells, Cultured; D003054:Cochlear Implants; D004558:Electric Stimulation / Q000379:methods*; D055590:Electromagnetic Phenomena; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000502:physiology; D013136:Spiral Ganglion / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium
keywords: Cochlear implant; Electrical stimulation; Neurite extension; Schwann cell; Spiral ganglion neuron; Voltage-dependent calcium channel