Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats.
Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats.
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DOI：
10.1002/cne.22582
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发表时间：
2011-06-01
影响因子：
2.5
通讯作者：
Stakhovskaya, Olga
中科院分区：
文献类型：
--
作者：
Leake, Patricia A.;Hradek, Gary T.;Hetherington, Alexander M.;Stakhovskaya, Olga
关键词：
螺旋神经节神经元的出生后发育和存活依赖于神经活动和神经营养支持。我们以前的研究表明，人工耳蜗电刺激只能部分防止早期耳聋后脑海马的变性。因此，可能与植入物结合以改善神经存活的神经营养剂是令人感兴趣的。最近的研究报道，BDNF促进耳聋后SG的存活，已在啮齿动物中进行，并限于相对较短的持续时间。我们的研究对耳聋猫进行了更长时间的脑源性神经营养因子治疗，这可能更好地模拟人类耳蜗神经节退行性变的缓慢进展，并首次提供了脑源性神经营养因子在发育中的听觉系统中的研究。新生猫致聋，4-5周龄时植入含有给药导管的耳壳内电极，从微型渗透泵中注入BDNF或人工外淋巴液10周。脑源性神经营养因子处理的耳蜗神经节细胞生长至正常大小，且明显大于对侧细胞。然而，它们的形态并不完全正常，许多神经元缺乏或已经变薄了核周髓鞘。无偏体视学被用来估计SG细胞密度，与细胞大小无关。脑源性神经营养因子能显著提高这些发育动物脑海马神经元的存活率。脑源性神经营养因子治疗后，有髓神经纤维密度增加，体积增大，纤维长入鼓阶，电诱发听性脑干反应阈值提高。尽管BDNF在发育中的听觉系统中可能具有潜在的治疗价值，但目前仍有许多严重的障碍阻碍了临床应用。
Postnatal development and survival of spiral ganglion (SG) neurons depend upon both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partly prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that BDNF promotes SG survival after deafness, have been conducted in rodents and limited to relatively short durations. Our study examined longer duration BDNF treatment in deafened cats that may better model the slow progression of SG degeneration in human cochleae and provides the first study of BDNF in the developing auditory system. Kittens were deafened neonatally, implanted at 4-5 weeks with intracochlear electrodes containing a drug-delivery cannula, and BDNF or artificial perilymph was infused for 10 weeks from a mini-osmotic pump. In BDNF-treated cochleae SG cells grew to normal size and were significantly larger than cells on the contralateral side. However, their morphology was not completely normal and many neurons lacked or had thinned perikaryl myelin. Unbiased stereology was employed to estimate SG cell density, independent of cell size. BDNF was effective in promoting significantly improved survival of SG neurons in these developing animals. BDNF treatment also resulted in higher density and larger size of myelinated radial nerve fibers, sprouting of fibers into the scala tympani, and improvement in electrically-evoked auditory brainstem response thresholds. Although BDNF may have potential therapeutic value in the developing auditory system, many serious obstacles currently preclude clinical application.
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影响因子：
1.4
作者：
ELVERLAND, HH;MAIR, IWS
通讯作者：
MAIR, IWS
影响因子：
--
作者：
Geers, AE
通讯作者：
Geers, AE
影响因子：
2.6
作者：
Endo, T;Nakagawa, T;Ito, J
通讯作者：
Ito, J
影响因子：
2.5
作者：
Kanzaki, S;Stöver, T;Raphael, Y
通讯作者：
Raphael, Y
12 个月以下接受人工耳蜗植入的儿童的沟通发展： 风险与益处
影响因子：
3.7
作者：
Dettman, Shani J.;Pinder, Darren;Leigh, Jaime R.
通讯作者：
Leigh, Jaime R.