COX-2 expression in the guinea pig cochlea is partly altered by moderate sound exposure.

The cyclooxygenase-2 isoform (COX-2) was found recently to be constitutively expressed in the guinea pig inner ear. To gain knowledge about its role in sound perception, alterations in the COX-2 level of moderate noise-stimulated cochleae were determined. Staining intensities were quantified in different regions using an immunohistochemical staining procedure and computer-assisted system. After 70 dB and 90 dB noise exposure for 1 h at 8000 Hz, COX-2 downregulation was observed in the organ of Corti, which was most prominent in Deiters' cells near Hensen cells and outer hair cells. In pillar cells, COX-2 levels were only slightly reduced after 70 dB but strongly diminished after 90 dB exposure. In Hensen cells, COX-2 was downregulated after 70 dB stimulation, revealing a decreasing COX-2 content from the third to the first turn of the cochlea and a homogeneously reduced enzyme expression in all three turns after 90 dB. The COX-2 content in inner hair cells was nearly identical to unexposed cochleae after 70 dB exposure but significantly reduced after 90 dB stimulation. In spiral ganglion cells, stria vascularis, spiral ligament and limbus, COX-2 expression was unchanged after 70 dB and 90 dB. We suggest that alterations in COX-2 expression might contribute to diminished sensitivity at the cochlea after noise exposure to reduce subsequent noise distress, termed sound conditioning.

Endothelial nitric oxide synthase upregulation in the guinea pig organ of Corti after acute noise trauma.

Endothelial nitric oxide synthase (eNOS) upregulation was identified 60 h after acute noise trauma in morphologically intact cells of the reticular lamina in the organ of Corti of the guinea pig in the second turn of the cochlea. Using gold-coupled anti-eNOS antibodies and electron microscopy, it was shown that eNOS expression was upregulated in all cell areas and cell types except inner hair cells. Furthermore, eNOS was found in the organelle-free cytoplasm and in mitochondria of various cell types. The density of eNOS in mitochondria was considerably higher compared with the surrounding cytoplasm. Since eNOS activity is regulated by calcium, the eNOS detection was combined with calcium precipitation, a method for visualizing intracellular Ca2+ distribution. After acute noise trauma, intracellular Ca2+ was increased in all cell types and cell areas except in outer hair cells. Comparing the distribution patterns of eNOS and calcium, significantly elevated levels (P < 0.0001) of eNOS were detected within a 100 nm radius near calcium precipitates in all cuticular structures as well as microtubule-rich regions and Deiters' cells near Hensen cells. The observed colocalization lends support to the postulated mechanism of eNOS activation by Ca2+. eNOS upregulation after acute noise trauma might therefore be part of an induced stress response. The eNOS upregulation in cell areas with numerous microtubule- and actin-rich structures is discussed with respect to possible cytoskeleton-dependent processes in eNOS regulation.