Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus.
Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus.
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DOI：
10.3171/2010.2.jns091817
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发表时间：
2011-02
影响因子：
4.1
通讯作者：
T. Sekiya;Masahiro Matsumoto;K. Kojima;Kazuya Ono;Y. Kikkawa;Shinpei Kada;H. Ogita;Rie T. Horie;Á. Viola;M. Holley;J. Ito
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文献类型：
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作者：
T. Sekiya;Masahiro Matsumoto;K. Kojima;Kazuya Ono;Y. Kikkawa;Shinpei Kada;H. Ogita;Rie T. Horie;Á. Viola;M. Holley;J. Ito
在接受显微手术治疗的前庭神经鞘瘤（VS）患者中，特别是在亚急性术后阶段，显微手术治疗后的听力水平逐渐恶化。这种迟发性听力恶化的原因还不完全清楚。本研究的目的是调查反应性胶质增生是一个促成因素的可能性。方法神经组织的机械损伤是复杂外科手术的一个特征。为了探讨VS治疗的这一方面，作者压迫大鼠听神经，造成2种不同程度的损伤，同时监测听神经的复合动作电位和听性脑干反应。在这个实验模型中，听觉神经的轴突在小脑桥脑角定量和高度选择性地受损，而不会永久损害耳蜗的血液供应。分别于加压后1周和8周取颞骨行免疫组化分析。结果机械性损伤后，不仅在听神经内，而且在耳蜗核内也可诱导反应性胶质增生，但听性脑干反应的总体形态保持不变。有大量的星形胶质细胞突起从过渡区到听神经的外周部分，导致在听神经中的致密胶质组织的入侵。延长的星形胶质细胞突起与残留的听觉神经元平行，并进一步进入耳蜗。共聚焦图像显示神经元碎片分散在神经胶质组织中。在耳蜗核，神经元索马周围有大量肥大的星形胶质细胞突起。压缩部位处和近端的听神经的横径显著减小，表明萎缩，特别是在听神经被深度压缩的大鼠中。结论：作者首次发现，对听神经的机械应力在1-8周内引起外周和中枢听觉通路的大量反应性胶质增生。手术应激后进行性反应性胶质增生可能导致听觉通路功能障碍，可能是VS显微手术治疗后进行性听力损失的主要原因。
OBJECT Hearing levels following microsurgical treatment gradually deteriorate in a number of patients treated for vestibular schwannoma (VS), especially in the subacute postoperative stage. The cause of this late-onset deterioration of hearing is not completely understood. The aim of this study was to investigate the possibility that reactive gliosis is a contributory factor. METHODS Mechanical damage to nerve tissue is a feature of complex surgical procedures. To explore this aspect of VS treatment, the authors compressed rat auditory nerves with 2 different degrees of injury while monitoring the compound action potentials of the auditory nerve and the auditory brainstem responses. In this experimental model, the axons of the auditory nerve were quantitatively and highly selectively damaged in the cerebellopontine angle without permanent compromise of the blood supply to the cochlea. The temporal bones were processed for immunohistochemical analysis at 1 week and at 8 weeks after compression. RESULTS Reactive gliosis was induced not only in the auditory nerve but also in the cochlear nucleus following mechanical trauma in which the general shape of the auditory brainstem response was maintained. There was a substantial outgrowth of astrocytic processes from the transitional zone into the peripheral portion of the auditory nerve, leading to an invasion of dense gliotic tissue in the auditory nerve. The elongated astrocytic processes ran in parallel with the residual auditory neurons and entered much further into the cochlea. Confocal images disclosed fragments of neurons scattered in the gliotic tissue. In the cochlear nucleus, hypertrophic astrocytic processes were abundant around the soma of the neurons. The transverse diameter of the auditory nerve at and proximal to the compression site was considerably reduced, indicating atrophy, especially in rats in which the auditory nerve was profoundly compressed. CONCLUSIONS The authors found for the first time that mechanical stress to the auditory nerve causes substantial reactive gliosis in both the peripheral and central auditory pathways within 1-8 weeks. Progressive reactive gliosis following surgical stress may cause dysfunction in the auditory pathways and may be a primary cause of progressive hearing loss following microsurgical treatment for VS.