Meniere's Disease Research Laboratory

Lab head: Daniel Brown
Location: The Brain & Mind Research Institute

This laboratory researches the cause of Meniere's Disease, a hearing and balance disorder characterized by random attacks of severe vertigo and fluctuating hearing loss.

It is currently thought that an abnormal volume of fluid in the inner ear called "endolymphatic hydrops" that can be seen in MRI scans causes a displacement of the inner ear hair cells that sense sound and orientation.

We are investigating the effects of endolymphatic hydrops, with the ultimate goal of understanding the mechanisms that lead to its production so that a cure can be developed.

Research approach equipment: In vivo electrophysiological studies in guinea pigs are used to investigate the effects of abnormal fluid volumes on inner ear function. These studies include conventional measurements of extracellular hair cell and neural electrical and mechanical responses to sound from the cochlea, as well as the development of novel measurement techniques for assessing vestibular hair cell responses to head rotations and displacements. The aim is to obtain simultaneous measurements of cochlear and vestibular hair cell displacement and function during various experimental manipulations that mimick Meniere's Disease.

Patuzzi, R.B., Brown, D.J., McMahon, C.M., Halliday, A.F. Determinants of the spectrum of the neural electrical activity at the round window: transmitter release and neural depolarisation. Hear Res. 2004.190(1-2): 87-108. PMID: 15051132

McMahon, C.M., Brown, D.J., Patuzzi, R.B. Transient focal cooling at the round window and cochlear nucleus shows round window CAP originates from cochlear neurones alone. Hear Res. 2004. 190(1-2): 75-6. PMID: 15051131

Brown, D.J., McMahon, C.M., Patuzzi, R.B. K+ currents produce P1 in the RW CAP: evidence from DC current bias, K+ channel blockade and recordings from cochlea and brainstem. Hear Res. 2004. 190(1-2): 60-74. PMID: 15051130

Brown DJ, Hartsock JJ, Gill RM, Fitzgerald HE, Salt AN. 2009. Estimating the operating point of the cochlear transducer using low-frequency biased distortion products. J Acoust Soc Am. 125(4):2129-45. PMID: 19354389

Salt AN, Brown DJ, Hartsock JJ, Plontke SK. 2009. Displacements of the organ of Corti by gel injections into the cochlear apex. Hear Res. 250(1-2):63-75. PMID: 19217935

Brown, D.J., Patuzzi R.B. 2010. Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater. Hear Res. 2010 Apr 26. [ahead of print] PMID: 20430085

Functional & Morphological changes resulting from Increased Blood- Labyrinth-Barrier Permeability

Primary supervisor: Daniel Brown

Like the Blood-Brain Barrier that limits fluid and molecule communication between cerebrospinal fluid and blood, the capillaries of the inner ear also have tight junctions that limit the communication between blood and inner ear fluid (perilymph) – the Blood-Labyrinth-Barrier (BLB). An immune response of the inner ear causes an increase in the BLB permeability, resulting in a moderate swelling of the membranous labyrinth and fluctuating hearing loss, and changes in the extracellular matrix proteins in the ear. This typically resolves within a week or so, and the inner ear recovers. It’s thought that in some people, this transient immune flare-up in the ear can permanently alter the ears fluid dynamics, resulting in a chronic build-up of fluid in various compartments. Which parts of the ear become damaged resulting in this build-up of fluid is not yet clear, but is vital to our understanding of Meniere’s Disease. Our laboratory is developing the tools and techniques, including in vivo electrophysiology and whole-mount post-mortem imaging, to investigate the long-lasting effects of immune challenges in the inner ear.

Discipline: Physiology
Co-supervisors: William Gibson
Keywords: Physiology, Hearing, Otolaryngology