Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus

Laboratory investigation

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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.

Abbreviations used in this paper: ABR = auditory brainstem response; CAP = compound action potential; CPA = cerebellopontine angle; CR = compression-recording; EDTA = ethylenediaminetetraacetic acid; GFAP = glial fibrillary acidic protein; IAA = internal auditory artery; IAC = internal auditory canal; IAM = internal auditory meatus; IPL = interpeak latency; PBS = phosphate-buffered saline; PNS = peripheral nervous system; TSF = tractus spiralis foraminosus; TZ = transitional zone; VS = vestibular schwannoma.
Article Information

Contributor Notes

Address correspondence to: Tetsuji Sekiya, M.D., Department of Otolaryngology, Head and Neck Surgery, Kyoto University Graduate School of Medicine, Sakyou-ku, Kyoto, 606-8507 Japan. email: tsekiya@ent.kuhp.kyoto-u.ac.jp.Please include this information when citing this paper: published online April 2, 2010; DOI: 10.3171/2010.2.JNS091817.
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