Histopathology in noise-induced hearing loss has been studied extensively in both mammalian and avian species. Although some of the earliest investigations of important structural changes in acoustic injury evaluated all structures of the inner ear, most recent attention has focused on damage to the sensory cells and neurons. It is clear that hair cell loss and stereocilia damage are fundamentally important in the etiology of chronic threshold shifts (Robertson and Johnstone 1980
; Robertson 1982
; Liberman and Dodds 1984
; Henderson et al. 1994
) and that excitotoxic damage to afferent neurons may contribute to acute threshold shifts (Robertson 1983
; Puel et al. 1998
). Much less is known about how damage to accessory structures, such as the stria vascularis and spiral ligament, contributes to noise-induced hearing loss in cases of either permanent threshold shift (PTS) or temporary threshold shift (TTS) caused by exposure to noise.
Although studied less extensively, structures of the lateral wall, i.e., the stria vascularis and the spiral ligament, can also be damaged by noise exposure or by aging (Liberman and Kiang 1978
; Gratton and Schulte 1995
; Gratton et al. 1996
; Spicer et al. 1997
; Ohlemiller et al. 1999
; Ichimiya et al. 2000
; Hequembourg and Liberman 2001
). In turn, lateral wall structures, in particular, the stria vascularis, are critical in maintaining ion homeostasis of the endolymph (Offner et al. 1987
; Salt et al. 1987
; Wangemann 1995
; Wangemann et al. 1995
; Takeuchi and Ando 1998
). The presence of Na/K–ATPases and Na/K/Cl cotransporters in the fibrocytes of the spiral ligament suggest that the ligament also plays a key role in the maintenance of the ionic environment and the endocochlear potential (Schulte and Adams 1989
; Spicer and Schulte 1996
; Crouch et al. 1997
). Previous studies have shown that noise exposure can lead to reductions in the EP (Vassout 1984
; Ide and Morimitsu 1990
; Wang et al. 1992
; Boettcher and Schmiedt 1995
; Ma et al. 1995
; Li et al. 1997
). Given the importance of the EP to normal cochlear sensitivity (Sewell 1984
), noise-induced histopathology in the lateral wall could contribute significantly to noise-induced hearing loss. If lateral wall structures do contribute to noise-induced hearing loss, then understanding the mechanisms underlying this damage could provide a novel method of intervention, independent of efforts to preserve hair cell integrity, and could potentially lead to strategies to prevent hearing loss after acoustic overstimulation.
Although previous studies have separately documented (1) noise-induced lateral wall histopathology, (2) noise-induced sensory cell damage, (3) noise-induced EP shifts, or (4) noise-induced threshold shifts, none has examined all four issues in the same ears. Similarly, no previous study has simultaneously examined all the cell types of the lateral wall which could be important to the generation and maintenance of normal EP and endolymphatic ionic composition, i.e., including both stria vascularis and spiral ligament. Thus, there are still a number of important unanswered questions, such as (1) whether EP shifts contribute to reversible threshold shifts or, alternatively, whether they appear only when the damage is severe enough to lead to a permanent loss; (2) whether noise-induced EP shifts, and the attendant threshold shifts, ever occur in ears in which the sensory cells and neurons have not been damaged; and (3) whether lateral wall degeneration correlates with loss of EP and whether EP loss is typically accompanied by visible histopathology in the lateral wall.
To address these questions, the present study assessed EP magnitude and cochlear threshold shifts, as well as light and electron microscopic histopathology of the lateral wall, in mice exposed to noise resulting in TTS in some groups and moderate to severe PTS in others. Survivals were 0 h to 8 weeks after noise exposure to provide insight into the dynamics of injury and repair.
The CBA/CaJ mouse was used as the animal model for a number of reasons. First, the genetic homogeneity of inbred strains such as CBA/CaJ is associated with less interanimal variability in the response to acoustic injury, allowing a clearer picture of injury dynamics to emerge from evaluation of groups sacrificed at a range of postexposure times (Ou et al. 2000
; Yoshida et al. 2000
; Wang et al. 2002
). Second, the availability of interesting transgenic mice in which particular genes have been knocked out or overexpressed is a powerful tool with which to study the mechanisms of acoustic injury (Ohlemiller et al. 1999
; Hakuba et al. 2000
; Prosen et al. 2000
). Third, our laboratory has recently completed a quantitative light microscopic evaluation of the noise-induced patterns of cellular damage and threshold shift in this mouse strain as function of postexposure survival following exposure to a wide range of sound levels (Wang et al. 2002
). This background information provides a valuable overview in which to consider the fine details of morphology revealed by the type of ultrastructural analysis used in the present study.