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Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid

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Abstract

Understanding how drugs are distributed in perilymph following local applications is important as local drug therapies are increasingly used to treat disorders of the inner ear. The potential contribution of cerebrospinal fluid (CSF) entry to perilymph homeostasis has been controversial for over half a century, largely due to artifactual contamination of collected perilymph samples with CSF. Measures of perilymph flow and of drug distribution following round window niche applications have both suggested a slow, apically directed flow occurs along scala tympani (ST) in the normal, sealed cochlea. In the present study, we have used fluorescein isothiocyanate-dextran as a marker to study perilymph kinetics in guinea pigs. Dextran is lost from perilymph more slowly than other substances so far quantified. Dextran solutions were injected from pipettes sealed into the lateral semicircular canal (SCC), the cochlear apex, or the basal turn of ST. After varying delays, sequential perilymph samples were taken from the cochlear apex or lateral SCC, allowing dextran distribution along the perilymphatic spaces to be quantified. Variability was low and findings were consistent with the injection procedure driving volume flow towards the cochlear aqueduct, and with volume flow during perilymph sampling driven by CSF entry at the aqueduct. The decline of dextran with time in the period between injection and sampling was consistent with both a slow volume influx of CSF (∼30 nL/min) entering the basal turn of ST at the cochlear aqueduct and a CSF-perilymph exchange driven by pressure-driven fluid oscillation across the cochlear aqueduct. Sample data also allowed contributions of other processes, such as communications with adjacent compartments, to be quantified. The study demonstrates that drug kinetics in the basal turn of ST is complex and is influenced by a considerable number of interacting processes.

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References

  • Adams J, Merchant S (2012) Cochlear lymphatics. Assoc Res Otolaryngol 35:159 (Abstract)

    Google Scholar 

  • Altmann F, Waltner JG (1947) The circulation of the labyrinthine fluids. Ann Oto Rhino Laryngo 56:684–708

    Article  CAS  Google Scholar 

  • Altmann F, Waltner JG (1950) Further investigations on the physiology of the labyrinthine fluids. Ann Otol 59:657–686

    CAS  Google Scholar 

  • Axelsson A, Ryan AF (2001) Circulation of the inner ear: I. Comparative study of the vascular anatomy of the mammalian cochlea. In: A.F. Jahn, J. Santos-Sacchi (eds) Physiology of the ear. Singular Press, San Diego, pp 301–320

  • Böhmer A (1993) Hydrostatic pressure in the inner ear fluid compartments and its effects on inner ear function. Acta Otolaryngol Suppl 507:3–24

    PubMed  Google Scholar 

  • Chen Z, Kujawa SG, McKenna MJ, Fiering JO, Mark JMJ, Borenstein JT, Swan EL, Sewell WF (2005) Inner ear drug delivery via a reciprocating perfusion system in the guinea pig. J Contrl Rel 110:1–19

    Article  CAS  Google Scholar 

  • Décory L, Franke RB, Dancer AL (1990) Measurement of the middle ear transfer function in cat, chinchilla and guinea pig. In: Dallos P, Geisler CD, Matthews JW, Ruggero MA, Steele CR (eds) The mechanics and biophysics of hearing. Springer, Berlin, pp 270–277

    Chapter  Google Scholar 

  • Ferrary E, Sterkers 0, Saumon O, Tran Ba Huy P, Amiel C (1987) Facilitated transfer of glucose from blood into perilymph in the rat cochlea. Am J Physiol 253:F59–F65

    CAS  PubMed  Google Scholar 

  • Gisselsson L (1949) The passage of fluorescein sodium to the labyrinthine fluids. Acta Oto!aryngol (Stockh) 37:268–275

    Article  CAS  Google Scholar 

  • Hara A, Salt AN, Thalmann R (1989) Perilymph composition in scala tympani of the cochlea: influence of cerebrospinal fluid. Hear Res 42:265–272

    Article  CAS  PubMed  Google Scholar 

  • Hirose K, Hartsock JJ, Johnson S, Santi P, Salt AN (2014) Systemic lipopolysaccharide compromises the blood-labyrinth barrier and increases entry of serum fluorescein into the perilymph. J Assoc Res Otolaryngol 15:707–719

    Article  PubMed  Google Scholar 

  • Kaupp H, Giebel W (1980) Distribution of marked perilymph to the subarachnoid space. Arch Otorhinolaryngal 229:245–253

    Article  CAS  Google Scholar 

  • Kimura RS, Schuknecht HF, Ota CY (1974) Blockage of the cochlear aqueduct. Acta Otolaryngol (Stockh) 77:1–12

    Article  CAS  Google Scholar 

  • Lawrence M, Wolks D, Litton WB (1961) Circulation of the inner ear fluids. Ann Otol 70:753–776

    CAS  Google Scholar 

  • Manni JJ, Kuijpers W (1987) Longitudinal flow of macromolecules in the endolymphatic space of the rat. An autoradiographical study. Hear Res 26:229–237

    Article  CAS  PubMed  Google Scholar 

  • Mynatt R, Hale SA, Gill RM, Plontke SKR, Salt AN (2006) Demonstration of a longitudinal concentration gradient along scala tympani by sequential sampling of perilymph from the cochlear apex. J Assoc Res Otolaryngol 7:182–193

    Article  PubMed Central  PubMed  Google Scholar 

  • Naftalin L, Harrison MS (1958) Circulation of labyrinthine fluids. J Laryngol 72:118–136

    Article  CAS  Google Scholar 

  • Ohyama K, Salt AN, Thalmann R (1988) Volume flow rate of perilymph in the guinea pig cochlea. Hearing Res 35(119):130

    Google Scholar 

  • Plontke SK, Mynatt R, Gill RM, Salt AN (2007) Concentration gradient along scala tympani following the local application of gentamicin to the round window membrane. Laryngoscope 117:1191–1198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Plontke SK, Biegner T, Kammerer B, Delabar U, Salt AN (2008) Dexamethasone concentration gradients along scala tympani after application to the round window membrane. Otol Neurotol 29:401–406

    Article  PubMed  Google Scholar 

  • Rask-Andersen H, Schrott-Fischer A, Pfaller K, Glueckert R (2006) Perilymph/modiolar communication routes in the human cochlea. Ear Hear 27:457–465

    Article  PubMed  Google Scholar 

  • Salt AN, DeMott JE (1998) Longitudinal endolymph movements induced by perilymphatic injections. Hear Res 123:137–147

    Article  CAS  PubMed  Google Scholar 

  • Salt AN, Ma Y (2001) Quantification of solute entry into cochlear perilymph through the round window membrane. Hear Res 154:88–97

    Article  CAS  PubMed  Google Scholar 

  • Salt AN, Thalmann R (1989) Rate of longitudinal flow of cochlear endolymph. In: Nadol JB (ed) Ménière’s disease. Kugler, Amsterdam, pp. 69 73

  • Salt AN, Kellner C, Hale S (2003) Contamination of perilymph sampled from the basal cochlear turn with cerebrospinal fluid. Hear Res 182:24–33

    Article  PubMed  Google Scholar 

  • Salt AN, Hartsock JJ, Gill RM, Piu F, Plontke SK (2012) Perilymph pharmacokinetics of markers and dexamethasone applied and sampled at the lateral semi-circular canal. J Assoc Res Otolaryngol 13(6):771–783

    Article  PubMed Central  PubMed  Google Scholar 

  • Sewell WF, Borenstein JT, Chen Z, Fiering J, Handzel O, Holmboe M, Kim ES, Kujawa SG, McKenna MJ, Mescher MM, Murphy B, Swan EE, Peppi M, Tao S (2009) Development of a microfluidics-based intracochlear drug delivery device. Audiol Neurootol 14:411–422

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Shepherd RK, Colreavy MP (2004) Surface microstructure of the perilymphatic space: implications for cochlear implants and cell- or drug-based therapies. Arch Otolaryngol Head Neck Surg 130:518–523

    Article  PubMed  Google Scholar 

  • Steel KP (1999) Perspectives: biomedicine. The benefits of recycling. Science 285:1363–1364

    Article  CAS  PubMed  Google Scholar 

  • Wit HP, Feijen RA, Albers FW (2003) Cochlear aqueduct flow resistance is not constant during evoked inner ear pressure change in the guinea pig. Hear Res 175:190–199

    Article  PubMed  Google Scholar 

  • Yimtae K, Song H, Billings P, Harris JP, Keithley EM (2001) Connection between the inner ear and the lymphatic system. Laryngoscope 111:1631–1635

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by research grant DC01368 from the National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH).

Conflict of Interest

The authors have no conflicts of interest with regard to this study.

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Authors and Affiliations

  1. Department of Otolaryngology, Washington University School of Medicine, Box 8115, 660, South Euclid Avenue, St. Louis, MO, 63110, USA

    A. N. Salt, R. M. Gill & J. J. Hartsock

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  1. A. N. Salt
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  2. R. M. Gill
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  3. J. J. Hartsock
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Correspondence to A. N. Salt.

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Salt, A.N., Gill, R.M. & Hartsock, J.J. Perilymph Kinetics of FITC-Dextran Reveals Homeostasis Dominated by the Cochlear Aqueduct and Cerebrospinal Fluid. JARO 16, 357–371 (2015). https://doi.org/10.1007/s10162-015-0512-1

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  • DOI: https://doi.org/10.1007/s10162-015-0512-1

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