Hearing preservation in Guinea pigs with long-standing endolymphatic hydrops.
OBJECTIVE
Interruption of the excitotoxic and inflammatory pathways implicated in endolymphatic hydrops (ELH)-associated hearing loss (HL) should afford hearing protection at the neuronal level.


BACKGROUND
Previous work in our laboratory in the mouse model of ELH shows that dimethyl sulfoxide (DMSO), an anti-inflammatory solvent, can slow the progression of HL before neuronal degeneration occurs. Riluzole, a glutamate release inhibitor, may provide synergistic benefit. This study was designed to quantify the effects of DMSO and riluzole in a long-term model.


METHODS
Guinea pigs with surgically induced ELH were sorted into 3 groups: riluzole+DMSO (Group 1), DMSO alone (Group 2), and untreated controls (Group 3). Animals in Groups 1 and 2 received daily injections of the study drug(s). All animals underwent auditory-evoked brainstem response evaluation every 4 weeks until 24 weeks, when they were sacrificed. Cochleae were preserved; spiral ganglion density was quantified. Animals without hydrops were excluded from the study as surgical failures.


RESULTS
Animals from all groups developed unilateral HL. At the end of the experiment, HL was significantly lower in Group 1 relative to Group 3 (p = 0.049) and trended toward lower in Group 2 relative to Group 3 (p = 0.097). Groups 1 and 2 were not different (p = 0.311). At the cellular level, there is no evidence of neuronal degeneration in either treated group, whereas there is a significant neuronal degeneration in the untreated group.


CONCLUSIONS
These results confirm the hearing protection observed with DMSO in short-term studies. However, unlike the previous study, which showed no additive benefit to riluzole, the combined treatment group in this study showed a hearing-protective effect at 24 weeks. This indicates a potential additive benefit conferred by riluzole toward long-term hearing protection. The study also finds evidence of statistically significant neuronal protection with both treatment groups. Overall, study provides additional evidence that DMSO and riluzole may preserve or slow the long-term progression of ELH-associated HL.
Department of Otolaryngology-Head and Neck Surgery, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
Suhael R
SR
Momin
Sami J
SJ
Melki
Joy O
JO
Obokhare
Souha A
SA
Fares
Maroun T
MT
Semaan
Cliff A
CA
Megerian
D000818:Animals; D003051:Cochlea / Q000473:pathology / Q000503:physiopathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology / Q000627:therapeutic use*; D018159:Endolymphatic Hydrops / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D019782:Riluzole; D004121:Dimethyl Sulfoxide