耳聋后延迟给予神经营养因子可挽救螺旋神经节细胞免于死亡,并促进听神经外周突再生:脑源性神经营养因子和成纤维细胞生长因子的作用
Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: effects of brain-derived neurotrophic factor and fibroblast growth factor.
作者信息
Miller Josef M, Le Prell Colleen G, Prieskorn Diane M, Wys Noel L, Altschuler Richard A
机构信息
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0506, USA.
出版信息
J Neurosci Res. 2007 Jul;85(9):1959-69. doi: 10.1002/jnr.21320.
The extent to which neurotrophic factors are able to not only rescue the auditory nerve from deafferentation-induced degeneration but also promote process regrowth is of basic and clinical interest, as regrowth may enhance the therapeutic efficacy of cochlear prostheses. The use of neurotrophic factors is also relevant to interventions to promote regrowth and repair at other sites of nerve trauma. Therefore, auditory nerve survival and peripheral process regrowth were assessed in the guinea pig cochlea following chronic infusion of BDNF + FGF(1) into scala tympani, with treatment initiated 4 days, 3 weeks, or 6 weeks after deafferentation from deafening. Survival of auditory nerve somata (spiral ganglion neurons) was assessed from midmodiolar sections. Peripheral process regrowth was assessed using pan-Trk immunostaining to selectively label afferent fibers. Significantly enhanced survival was seen in each of the treatment groups compared to controls receiving artificial perilymph. A large increase in peripheral processes was found with BDNF + FGF(1) treatment after a 3-week delay compared to the artificial perilymph controls and a smaller enhancement after a 6-week delay. Neurotrophic factor treatment therefore has the potential to improve the benefits of cochlear implants by maintaining a larger excitable population of neurons and inducing neural regrowth.
神经营养因子不仅能够挽救听觉神经使其免于去传入诱导的退变,还能促进其突起再生,这一作用程度具有基础和临床研究价值,因为再生可能会提高人工耳蜗的治疗效果。神经营养因子的应用也与促进神经创伤其他部位再生和修复的干预措施相关。因此,在豚鼠耳蜗中,于鼓阶慢性输注脑源性神经营养因子(BDNF)+成纤维细胞生长因子1(FGF(1))后,评估听觉神经的存活情况及外周突起再生情况,治疗在致聋去传入后4天、3周或6周开始。从蜗轴中部切片评估听觉神经胞体(螺旋神经节神经元)的存活情况。使用泛原肌球蛋白受体激酶(pan-Trk)免疫染色选择性标记传入纤维来评估外周突起再生情况。与接受人工外淋巴的对照组相比,每个治疗组均观察到显著增强的存活情况。与人工外淋巴对照组相比,BDNF + FGF(1)治疗在延迟3周后外周突起有大量增加,延迟6周后增强程度较小。因此,神经营养因子治疗有可能通过维持更大数量的可兴奋神经元群体并诱导神经再生来改善人工耳蜗的益处。