Hair Cell Recovery in the Chinchilla Crista Ampullaris after Gentamicin Treatment: A Quantitative Approach

Abstract

The mechanisms for hair cell recovery were investigated after intraortic application of 50 microg gentamicin into the perilymphatic space of the superior semicircular canal of the chinchilla. Histologic evaluation of one normal group and four posttreatment groups (7, 14, 28, and 56 days) was made with light and transmission electron microscopic techniques. The numeric changes of hair cells and supporting cells was quantified with the dissector technique. At 7 and 14 days after treatment, no type I hair cells were present, and 85% and 88% of type II hair cells were lost. Supporting cells decreased to 76% at 7 days, but they recovered to 91% at 14 days. Recovery of the epithelia was evident 28 days after treatment; 83% were type II hair cells, and 3% were type I hair cells. The supporting cell number remained close to normal (86%). Between 14 and 28 days after treatment, there was an increase of 1758 of type II hair cells, representing approximately 125 new hair cells per day. At the same time interval the number of supporting cells remained near normal. These results suggest that new hair cells might be the result of supporting cell mitotic division and differentiation.

Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function

“…It is quite possible that both a regenerative cell proliferative response to treatment with growth factors (21,47) and transdifferentiation of existing support cells (11) contribute to our observed HC renewal results. Previous studies without trophic factor infusion therapy (11,29,42) have reported a recovery of type 2 vestibular HCs (Ͼ50%), but almost no recovery of type 1 HCs (Յ5%). In the present study, the observed recovery of HVOR function after GF II therapy is associated with the recovery of type 1 HCs in the damaged cristae.…”

“…The replacement of lost HCs in the avian vestibule is thought to involve a proliferative response (2)(3)(4). Although the results of an in vitro study (41) analyzing mammalian vestibular HC regeneration do not support a proliferation-mediated mechanism, the results of an in vivo study (42) do suggest cell proliferation. There is in vivo evidence that existing vestibular support cells can transdifferentiate into replacement hair cells (11,43).…”

Synaptophysin Immunohistochemistry during Vestibular Hair Cell Recovery after Gentamicin Treatment

“…The number of hair cells recovered to 58% with a recovery of SSA to 54% of normal. These results suggest that a greater fraction of synaptophysin expression within the sensory epithelium depends on the presence of afferent calyceal endings, which areIntroduction Vestibular hair cell regeneration in fish, amphibians, birds and mammals (including humans) has been demonstrated in a variety of experimental conditions [Baird et al, 1993;Carranza et al, 1994;Forge et al, 1993Forge et al, , 1998Lopez et al, 1997Lopez et al, , 1998Lopez et al, , 1999Honrubia et al, 2001, Kuntz andOesterle, 1998;Lombarte et al, 1993;Tanyeri et al, 1995;Warchol et al, 1993;Weisleder and Rubel, 1993;Wilkins et al, 1999]. One aspect of this phenomenon, the process of reinnervation of the recovering vestibular hair cells, has not been examined in detail, yet it is crucial in understanding the physiological recovery of hair cells and inner ear function [Henning and Cotanche, 1998;Cotanche, 1999].…”

“…One experimental approach to study vestibular hair cell regeneration has been the use of gentamicin ototoxicity to destroy hair cells after intraotic treatment of gentamicin in the vestibule of chinchillas [Tanyeri et al, 1995;Lopez et al, 1997Lopez et al, , 1998]. The temporal sequence of the morphological changes in the crista of the horizontal semicircular canal subsequent to intraotic treatment with 0.05 mg gentamicin can be divided into 3 phases [Lopez et al, 1998]: phase 1 = degeneration -during the 2 weeks immediately after treatment, characterized by destruction of all type I hair cells, 85% of type II hair cells and 24% of supporting cells; nerve terminals swell and retract from the sensory epithelia; phase 2 = restoration -during the third week after treatment, marked by recovery to nearnormal values of type II hair cells (83%) and supporting cells (91%); blunt-ended nerve terminals return to the sensory epithelium after penetrating the basal membrane from the stroma; phase 3 = maintenance -taking place from 4 weeks and beyond after treatment (i.e.…”

“…The temporal sequence of the morphological changes in the crista of the horizontal semicircular canal subsequent to intraotic treatment with 0.05 mg gentamicin can be divided into 3 phases [Lopez et al, 1998]: phase 1 = degeneration -during the 2 weeks immediately after treatment, characterized by destruction of all type I hair cells, 85% of type II hair cells and 24% of supporting cells; nerve terminals swell and retract from the sensory epithelia; phase 2 = restoration -during the third week after treatment, marked by recovery to nearnormal values of type II hair cells (83%) and supporting cells (91%); blunt-ended nerve terminals return to the sensory epithelium after penetrating the basal membrane from the stroma; phase 3 = maintenance -taking place from 4 weeks and beyond after treatment (i.e. 8 weeks), when the numbers of type II hair cells and supporting cells regain a stable equilibrium, with at least partial recovery of synapses as documented with transmission electron microscopy.…”