Functional and Morphological characterization of NOD-SCID inner ear

OBJECTIVE. Sensorineural hearing impairment is a consequence of hair cells (HC) and/or spiral ganglion neurons loss. In mammals, HCs are unable to regenerate, so their loss cause irreversible damages. For this reason it is very important to study the mechanisms to stimulate cochlear tissues regeneration with stem cells. Moreover it is necessary to choose the correct animal model. The NOD-SCID is a mouse with hampered immune system useful for stem cells transplantation, but there are no information about its auditory capacity. The aim of the project is to characterize the functionality and the morphology of the NOD-SCID inner ear because it derives from NOD mouse which presents a progressive hearing loss. METHODS. Animal models: 4-8-12 week-old CBA/J (non hearing-impaired), NOD (hearing-impaired) and NOD-SCID. Investigations: electrophysiology (ABR), histology of cochlea, spleen and tongue. All tissues were fixed, paraffin-embedded, and the sections were Hematoxylin-Eosin stained. The cochleae were cut into ten series of slides with sequential sections (thick 5um), for each section we evaluated inner and outer hair cells number, neuronal density, stria vascularis (SV) area and spiral ligament (SL) area. The percentage of fungiform and filiform papillae was counted along the superficial side of the tongue sections (1). The morphological changes of red and white pulp of the spleen were studied. All data were analyzed with ANOVA Bonferroni\u2019s test. RESULTS. NOD-SCID mice show a progressive hearing impairment at high frequencies from 4 to 12 weeks. The deafness appears to be associated with hair cells loss in the medium/basal region of the cochlea, likely as a consequence of SV and SL morphological and functional alterations. The histological study of NOD-SCID tongue demonstrates abnormalities in the organ development and an erythroid cells accumulation is observed in the spleen red pulp. CONCLUSIONS. Deafness of NOD-SCID mice could be due to premature aging, or could be a consequence of physiological/metabolic alterations that interfere with Organ of Corti functionality causing hair cells death