Effects of BDNF and NT-3 on hair cell survival in guinea pig cochlea damaged by kanamycin treatment

Abstract

The aim of this study was to determine whether neurotrophic factors such as brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) would protect auditory hair cells from ototoxicity by aminoglycoside antibiotic. Twenty-seven Wistar guinea pigs were divided into three groups of nine animals each. BDNF and NT-3 (100 microg/ml) were delivered into the right scala tympani of guinea pig cochlea through a cannula-osmotic pump device. Artificial perilymph (AP) was used as control. Immediately after implantation of the device, each animal was given five successive doses of kanamycin (400 mg/kg). At 15, 30 and 60 days after infusion, surviving inner and outer hair cells were counted at each turn of every cochlea with a Philips 515 scanning electron microscope. Multiple comparison tests were carried out among the groups, using ANOVA and Dunnett T3/Tukey HSD. Protective effects of NT-3 on hair cells were observed at 30 and 60 days after kanamycin injection. BDNF had no protective effect on hair cells at 15 and 60 days, but some at 30 days. This study suggests that NT-3 and BDNF may protect against cochlear hair cell damage caused by kanamycin treatment. Possible mechanisms for the otoprotective effects were discussed. No single mechanism postulated can explain fully the results seen in this study. It is possible that the mechanisms act in concert to produce the observed effects, or there are as yet undiscovered mechanisms or secondary messengers responsible for the otoprotective effects.

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

“…152 Indeed, the survival effects of BDNF on neuronal cells were not observed after the treatment phase. 155 This phenomenon has been widely confirmed by other studies in different neural systems, indicating that the survival effects of BDNF, as well as other growth factors only last so long as the treatment itself.…”

“…Meanwhile, another study claimed that BDNF had no protective effect on HCs at 15 days (total 9 μg of BDNF) and 60 days (36 μg), but some effects at 30 days (18 μg). 152 One more study demonstrated that direct placement of 0.05 μg of BDNF into the inner ear after cochleostomy did not improve or treat hearing loss after cisplastin-induced deafening. 148 At the same time, the positive effect of 8.4 ng BDNF on SGCs survival in deaf guinea pigs has remained controversial in the context of dose-dependent manner of BDNF action.…”

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig

“…While, this approach is invasive and would be of considerable clinical risk, in experimental animal studies, the use of the osmotic pump has been demonstrated effective in the delivery of neurotrophic factors (Miller et al, 1997;Ylikoski et al, 1998;Ruan et al, 1999;Shoji et al, 2000a,b;Shinohara et al, 2002), viral vectors (Yagi et al, 1999), antioxidants (Yamasoba et al, 1998;Ohinata et al, 2000a,b), and transmitter antagonists (Ohinata et al, 2003;Puel et al, 1998;Jager et al, 2000). We have used this methodology in the recent demonstration of GCÕs effective protection of the inner ear from aminoglycoside ototoxicity (Himeno et al, 2002).…”

A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support

“…When given prior to or simultaneous to deafening, there is up to 95% survival of SGNs and hair cell protection (Ernfors et al, 1996;Ruan et al, 1999;Yagi et al, 1999;Suzuki et al, 2000). When given 4-7 days after deafening, 78-100% of SGNs survive (Staecker et al, 1996(Staecker et al, , 1998Miller et al, 1997;Yagi et al, 2000;Shinohara et al, 2002;Gillespie et al, 2003).…”