DESCRIPTION: Labyrinthitis ossificans (LO) is the growth of pathologic new bone within the lumen of the cochlea. It is multifactorial in origin and may result in deafness. Profound hearing loss and LO in children are most commonly associated with meningogenic labyrinthitis. The relationship of LO to meningogenic cochlear pathology and its mechanism of induction have not been clearly defined. Cochlear implants are a significant treatment option for improving hearing and quality of life in these patients. However, LO can reduce the efficacy of cochlear implantation. The long-term objective of this research program is to understand the mechanisms which lead to the development, progression, and destructive aspects of LO. Such an understanding may lead to new strategies to prevent the devastating effects of hearing loss associated with this disease. The specific aims of this application are: (1) to correlate hearing loss with the temporal and spatial progression of bacterial meningitis from the subarachnoid space to the cochlea; (2) to correlate hearing loss with the temporal and spatial sequence for both labyrinthine fibrosis and ossification and the histopathology of cochlear tissues: spiral ganglion, organ of Corti, Reissner's membrane, stria vascularis, and spiral ligament; (3) to determine the relationship of bone lining cells to osteoblast formation and recruitment during labyrinthine neo-ossification; and (4) to determine the effects of decomplementation, non-steroidal anti-inflammatory compounds, and bacteriostatic vs. bactericidal antibiotics on neo-ossification and hearing loss. There are four hypotheses/specific aims outlined and they are as follows: Bacterial invasion of the cochlear labyrinth from the subarachnoid space correlates with hearing loss and occurs principally via the cochlear aqueduct and not the internal auditory canal; The destruction of cochlear tissue occurs subsequent to the arrival of inflammatory cells and not with the appearance of bacteria within the cochlea. Hearing loss may occur prior to observable pathology and reflect central auditory damage related to meningitis; Bone lining cells of the endosteum are activated and become mature osteoblasts and are the principal source of neo-ossification in labyrinthitis ossificans; and The inflammatory response to suppurative labyrinthitis includes fibrosis and neo-ossification formation and causes cochlear tissue destruction. Inhibition of this process will result in a reduction in both hearing loss and bone deposition. Methods used: The investigators propose to use an experimental gerbilline model of LO, histomorphometry, fluorescent bone histomorphometry, transmission and scanning electron microscopy, autoradiography, and auditory brainstem evoked response.
|Effective start/end date||1/1/00 → 12/31/05|
- National Institutes of Health: $331,237.00
- National Institutes of Health: $251,067.00
- National Institutes of Health: $235,592.00
- National Institutes of Health: $242,632.00
- National Institutes of Health: $256,091.00