|Budget Amount *help
¥2,300,000 (Direct Cost : ¥2,300,000)
Fiscal Year 1998 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1997 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
1) Experimental labyrinthitis was induced in guinea pigs by inocultation of keyhole limpet hemocyanin (KLH) into the scala tympani after sysytemic sensitization of the same antigen. The inner ears in the animal models were investigated histologically. Inflammatory cells, some of which contained KLH, were observed in the scala tympani, spiral modiolar vein (SMY) and its collecting venule (CV). SMV, spiral ligament and spiral limbus were diffusely positive for IgG and albumin, although lgG-positive plasma cells were hardly detected. The endolymphatic sac showed no increase in number of immunocompetent cells. We previously reported the expression of intercellular adhesion molecule-1 (ICAM-1) not only on the SMVand CVs but also on the spiral ligament. These data, take together, suggest that the inflammatory cells seen in the cochlea in this animal model were mainly due to extravasation from blood vessels rather than infiltration from the endolymphatie sac. In addition, immunoreactivity for
connexin 26 and sodium-potassium adenosine triphosphate was decreased in the fobrocytes of the spiral ligament. The results suggest that fibrocyte damage in the spiral ligament could cause cochlear dysfunction.
2) Cultures from murine spiral ligament fibrocytes were stimulated by interleukin (IL)-1b or tumor necrosis factor (TNF)-a, and secretion of various mediators was measured by enzyme-linked immunosorbent assay. After stimulation with the proinflammatory cytokines, IL-6, TNF-a, monocyte chemoattractant protein-1, KC, macrophage inflammatory protein-2, soluble ICAM-1, and vascular endothelial growth factor levels were elevated. Secretion of these chemokines and other mediators could induce inflammatory, cell movement, which wound prolong the inflammatory response, leading to fibrocyte damage. Given that spiral ligament fibrocytes may play a role in cochlear fluid and ion homeostasis, such fibrocyte disruption could cause cochlear malfunction.
3) The cochlear influence of otitis media was investigated in order to identify damaged regions causing cochlear malfunction. Otitis media in BALB/c mice was induced by injection of viable Streptococcus pneumoniae into the middle ear cavity for immunohistochemical analysis. Some animals showed inflammatory cells in the cochlea. Immunohistochemistry showed the presence of fibrinogen in the cochlea, mainly in the lower portion of the spiral ligament and in the spiral limbus. Immunostaining for connexin 26 was decreased in the spiral ligament, accompanied by remarkable fibrinogen staining. The presence of fibrinogen in the cochlea suggests disruption of the blood-labyrinth barrier caused by the middle ear inflammation. Changes in connexin 26 staining suggest the possibility that the spiral ligament could be among the regions responsible for the cochlear malfunction. Less