TY - JOUR
T1 - Drug delivery into the cochlear apex
T2 - Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral
AU - Lichtenhan, J. T.
AU - Hartsock, J.
AU - Dornhoffer, J. R.
AU - Donovan, K. M.
AU - Salt, A. N.
N1 - Funding Information:
We thank Professor John J. Guinan Jr., Dr. Uzma S. Wilson, and Dr. Spencer B. Smith for their productive criticisms on an early version of this manuscript. This work was supported by R01 DC014997 (J.T.L.) and R01 DC001368 (A.N.S.) from the National Institutes of Health , National Institute on Deafness and Other Communication Disorders .
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Background Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears. New method Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate. Results Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time. Conclusions Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.
AB - Background Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears. New method Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate. Results Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time. Conclusions Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.
KW - Auditory nerve overlapped waveform
KW - Cochlear action potential
KW - Cochlear fluid
KW - Cochlear perfusion
KW - Kainic acid
UR - http://www.scopus.com/inward/record.url?scp=85027938606&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2016.08.005
DO - 10.1016/j.jneumeth.2016.08.005
M3 - Article
C2 - 27506463
AN - SCOPUS:85027938606
SN - 0165-0270
VL - 273
SP - 201
EP - 209
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
ER -