Miller J M, Chi D H, O'Keeffe L J, Kruszka P, Raphael Y, Altschuler R A
Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506, USA.
Int J Dev Neurosci. 1997 Jul;15(4-5):631-43. doi: 10.1016/s0736-5748(96)00117-7.
Following destruction of sensory cells of the organ of Corti, spiral ganglion cells (SGC) in the guinea pig degenerate. Chronic electrical stimulation via cochlear prostheses can enhance their survival, with the effect blocked by stopping the electrically elicited action potentials with tetrodotoxin. Blocking action potentials in the normal hearing ear with tetrodotoxin, however, does not cause degeneration. This suggests that in the pathological ear VIII N activity acts as a survival factor, while in the normal ear there are other survival factors that maintain SGCs. We examined neurotrophins, as survival factors in the deafened ear. Two weeks of treatment with BDNF (brain derived neurotrophic factor) administered chronically via a mini-osmotic pump into scala tympani at 50 ng/ml, provided a statistically significant enhanced SGC survival over untreated deafened ears or deafened ears treated with artificial perilymph. Neurotrophin 3 provided some enhanced survival, but this was not statistically significant over untreated deafened ears. These observations suggest there are survival factors in the inner ear, including those coupled to direct activation of the auditory nerve fibers, that may serve to maintain the auditory nerve. These factors may be applied following deafness to maintain and enhance neural populations and to increase benefits to the profoundly deaf receiving cochlear implants.
在豚鼠的柯蒂氏器感觉细胞被破坏后,螺旋神经节细胞(SGC)会发生退化。通过人工耳蜗进行慢性电刺激可提高其存活率,而用河豚毒素阻断电诱发的动作电位会阻止这种效果。然而,用河豚毒素阻断正常听力耳朵的动作电位并不会导致退化。这表明在病理状态的耳朵中,第八对脑神经(VIII N)的活动起到了存活因子的作用,而在正常耳朵中存在其他维持螺旋神经节细胞的存活因子。我们研究了神经营养因子作为耳聋耳朵中的存活因子。通过微型渗透泵以50 ng/ml的浓度向鼓阶慢性给药脑源性神经营养因子(BDNF)两周,与未治疗的耳聋耳朵或用人工外淋巴治疗的耳聋耳朵相比,螺旋神经节细胞的存活率有统计学意义的显著提高。神经营养因子3也使存活率有所提高,但与未治疗的耳聋耳朵相比,这一提高没有统计学意义。这些观察结果表明,内耳中存在存活因子,包括那些与听神经纤维直接激活相关的因子,它们可能有助于维持听神经。这些因子可在耳聋后应用,以维持和增强神经群体,并增加对接受人工耳蜗植入的极重度耳聋患者的益处。
Int J Dev Neurosci. 1997-7
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