Journal Club: Surgical approach to collect 1 microliter of perilymph from gerbil cochlea.

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Today's journal article

Olivier C, Beck C, Risoud M, Lemesre PE, Siepmann J, Siepmann F, Vérin J, Goossens JF, Kouach M, Bongiovanni A, Hubert T, Tardivel M, Vincent C, Toulemonde P. Perilymph sampling in Mongolian gerbil, technical note and procedure evaluation. 

Why I picked this article

There are many compounds being tested to develop therapies for preventing or reversing the pathology of hearing loss. However, challenges remain in how to deliver such therapy to the inner ear site of pathology, the cochlea. Intratympanic injection is a clinical procedure where a drug is injected through the eardrum into the middle ear with a needle. From there, the drug diffuses across the round‑window membrane into the cochlea, into the perilymph. The pharmacokinetics of how drug concentration in the cochlea changes, and how they are cleared from the cochlea, is largely unknown currently. 

This research describes and evaluates an approach to sample perilymph from the cochlea, to conduct such research. 

Some of the research findings

Animal model:
  • Mongolian gerbil (Meriones unguiculatus), 8-12 months old x 12 animals. 
  • Cochlear context: 11 animals had intracochlear implants pre‑loaded with dexamethasone in scala tympani; 1 animal served as a non‑implanted control.
  • Cylindrical implant -= 2 mm long and 300 μm in diameter
    • non-absorbable implant made of ethylene-vinyl-acetate polymer matrix, loaded with 20% dexamethasone. 
    • absorbable implant made of poly-lactic-co-glycolic polymer matrix loaded with 20@ dexamethasone.
  • After animals were implanted, animals went through perilymph sampling procedure. 
Perilymph sampling: 
  • Access: submandibular route to the bulla; external ear canal, tympanic membrane, and ossicles were sacrificed to fully expose the cochlea. 
  • Stapes was carefully cut so that the stape's footplate stay in place and the perilymph does not leak out. 
  • Silicon cup was placed over the apical turn of the cochlear otic capsule. This allows collection of perilymph. 
  • A hole was made at the apex, and the fluid was collected using the microcapillary tube. 
  • The capillaries used (3 μL microcapillary; MicroCaps; Drummond, USA) 
  • The length of capillaries were adjusted so that  1 μL sample was collected. 
Observations from the procedure:
  • Contamination: frequent blood contamination from otic‑capsule bleeding at the cochleostomy was observed in the collected perilymph ( 74% of the time). 
  • Dexamethasone concentrations ranged from 1450 to 48 ng/mL (over 54 days) and from 472 to 0 ng/mL (over 40 days), respectively, from implant types. 
  • The detailed data and analysis will be published in a subsequent publication (out of scope of this publication) 
  • Tissue effects: fibrosis could develop along the labyrinth after a sampling event; this reduced the quality/reliability of any subsequent sampling attempts in the same ear.
Part of Figure 3B. Fibrosis after repeated sample collection. Olivier et al. 2025. 

Haruna's takeaway

This is a valuable study trying to establish the cochlear pharmacokinetics in the perilymph. This publication focuses on the surgical approach only, and it appears that the analysis of the dexamethasone concentration will be shared in a separate research publication. I will look forward to reading the follow-up publication, which details the pharmacokinetic analysis. 

Blood contamination is a very real risk, regardless of the animal models for sampling from the inner ear. Even after surgically exposing the organ, it's too easy to get blood contamination. This has been an issue with injection, too, in our sheep model, as the needle can scratch the skin anywhere and cause bleeding. How to be minimally invasive and not cause bleeding is a big challenge 

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This is Haruna's 71/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.