A Once-Daily High Dose of Intraperitoneal Ascorbate Improves Vestibulo-ocular Reflex Compensation After Unilateral Labyrinthectomy in the Mouse

Serajul I Khan; Alan M Brichta; Americo A Migliaccio

doi:10.1007/s10162-021-00831-1

A Once-Daily High Dose of Intraperitoneal Ascorbate Improves Vestibulo-ocular Reflex Compensation After Unilateral Labyrinthectomy in the Mouse

J Assoc Res Otolaryngol. 2022 Feb;23(1):27-34. doi: 10.1007/s10162-021-00831-1. Epub 2022 Jan 3.

Authors

Serajul I Khan^{1

2}, Alan M Brichta³, Americo A Migliaccio^{4

5

6

7}

Affiliations

¹ Balance and Vision Laboratory, Neuroscience Research Australia, Sydney, NSW, 2031, Australia.
² University of New South Wales, Sydney, NSW, 2033, Australia.
³ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
⁴ Balance and Vision Laboratory, Neuroscience Research Australia, Sydney, NSW, 2031, Australia. a.migliaccio@neura.edu.au.
⁵ University of New South Wales, Sydney, NSW, 2033, Australia. a.migliaccio@neura.edu.au.
⁶ School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia. a.migliaccio@neura.edu.au.
⁷ Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, 21205, USA. a.migliaccio@neura.edu.au.

Abstract

Ascorbate potentiates the response of nicotinic-acetylcholine-receptors containing α9 and α10 subunits found predominantly in the efferent systems of the inner ear, such as the efferent vestibular system (EVS). Prior mouse studies have shown that an attenuated EVS results in reduced vestibulo-ocular reflex (VOR) gain (=eye_velocity/head_velocity) plasticity in intact (VOR adaptation) and surgically-lesioned (VOR compensation) mice. We sought to determine whether ascorbate-treatment could improve VOR recovery after vestibular organ injury, possibly through potentiation of the EVS pathway. We tested 10 cba129 mice, 5 received ascorbate-treatment and 5 did not, but otherwise experienced the same conditions. Ascorbate-treatment comprised a once-daily intraperitoneal injection of L-form reduced ascorbate (4 g/kg) in 0.2 ml saline starting 1 week before, and ending 4 weeks after, unilateral labyrinthectomy surgery. These were deliberately high doses to determine the ascorbate effects on recovery. Baseline, acute, and chronic sinusoidal VOR gains (frequency and velocity ranges: 0.2-10 Hz, 20-100 deg/s) were measured 3-5 days before, 3-5 days after, and 28-31 days after labyrinthectomy. Mice treated with ascorbate had acute ipsilesional VOR gains 12 % higher compared to control mice (+45.2 ± 14.9 % from baseline versus +33.7 ± 15.4 %, P < 0.001). Similarly, chronic ipsilesional and contralesional VOR gains were respectively 16 % (+74.3 ± 16.3 % from baseline versus +58.1 ± 15.8 %, P < 0.001) and 13 % (+78.6 ± 16.0 % versus +65.6 ± 10.9 %, P < 0.001) higher compared to control mice. These data suggest ascorbate-treatment had a prophylactic effect reducing acute loss, and helped recovery during acute to chronic stages of compensation. One possible mechanism is that an ascorbate-enhanced EVS drives an increase in the number and sensitivity of irregular-discharging primary vestibular afferents, important for VOR plasticity.

Keywords: ascorbate; efferent vestibular system; vestibular compensation; vestibular plasticity; vestibulo-ocular reflex.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Physiological / physiology
Animals
Efferent Pathways
Mice
Reflex, Vestibulo-Ocular* / physiology
Vestibule, Labyrinth* / physiology