Maruyama Jun, Miller Josef M, Ulfendahl Mats
Center for Hearing and Communication Research, Karolinska Institutet, Sweden.
Neurobiol Dis. 2008 Jan;29(1):14-21. doi: 10.1016/j.nbd.2007.07.026. Epub 2007 Aug 11.
Cochlear implant surgery is currently the therapy of choice for profoundly deaf patients. However, the functionality of cochlear implants depends on the integrity of the auditory spiral ganglion neurons. This study assesses the combined efficacy of two classes of agents found effective in preventing degeneration of the auditory nerve following deafness, neurotrophic factors, and antioxidants. Guinea pigs were deafened and treated for 4 weeks with either local administration of GDNF or a combination of GDNF and systemic injections of the antioxidants ascorbic acid and Trolox. The density of surviving spiral ganglion cells was significantly enhanced and the thresholds for eliciting an electrically evoked brain stem response were significantly reduced in GDNF treated animals compared to deafened-untreated. The addition of antioxidants significantly enhanced the evoked responsiveness over that observed with GDNF alone. The results suggest multiple sites of intervention in the rescue of these cells from deafferentation-induced cell death.
人工耳蜗植入手术目前是极重度耳聋患者的首选治疗方法。然而,人工耳蜗的功能取决于听觉螺旋神经节神经元的完整性。本研究评估了两类已被发现对预防耳聋后听神经退变有效的药物——神经营养因子和抗氧化剂的联合疗效。将豚鼠致聋,并用局部给予胶质细胞源性神经营养因子(GDNF)或GDNF与抗氧化剂抗坏血酸和生育三烯酚全身注射的组合进行4周治疗。与未治疗的致聋动物相比,接受GDNF治疗的动物中存活的螺旋神经节细胞密度显著增加,诱发电诱发脑干反应的阈值显著降低。添加抗氧化剂后,诱发反应性比单独使用GDNF时显著增强。结果表明,在从去传入诱导的细胞死亡中挽救这些细胞方面存在多个干预位点。