Table 1.
Effects of BDNF and NT3 in the Mammalian Inner Ear-Literature Review Highlights.
| Authors | Year of Pub. |
NTF Used |
Animal Model |
Control | Method of Admin. |
Timing of Admin. |
Effects of Neurotrophin Treatment |
|---|---|---|---|---|---|---|---|
| Staecker et al. | 1996 | BDNF, NT3 | Guinea pig | -Deafened, untreated -Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -8 week infusion |
-SGN: Increased SGN survival rate with BDNF, NT3, or both |
| Ernfors et al. | 1996 | NT3 | Guinea pig | -Deafened, untreated -Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -2 week infusion |
-SGN: Increased SGN survival rate -PAF: Re-growth of neurofibers -ABR: No significant change in eABR threshold |
| Miller et al. | 1997 | BDNF, NT3 | Guinea pig | -Deafened, untreated -Deafened AP -Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -2 week infusion |
-SGN: Complete rescue of SGNs with BDNF; No statistically significant effect induced by NT3 |
| Staecker et al. | 1998 | BDNF | Mouse | -Deafened, untreated -Normal hearing |
-Viral vector (HSV-1) -Scala Tympani |
-Post-deafening -4 week casette expression |
-SGN: Almost complete rescue of SGNs |
| Ruan et al. | 1999 | BDNF, NT3 | Guinea pig | -Deafened, AP | -Mini-osmotic pump -Scala Tympani |
-Pre-deafening -15, 30 or 60 days infusion |
-IHC: Protected from ototoxic lesion with 30 days BDNF treatment or with NT3 treatment -OHC: Protected from ototoxic lesion with NT3 treatment |
| Shoji et al. | 2000 | BDNF, NT3 | Guinea pig | -Deafened, AP | -Mini-osmotic pump -Scala Tympani |
-Pre-deafening×4 days -----OR----- -Post-deafening×1 week |
-OHC: Protected from noise induced lesion with NT3 treatment; Not protected with BDNF treatment -ABR: eABR threshold lowered significantly for ototoxin exposed ear after neurotrophin treatment in a concentration dependent manner |
| Shinohara et al. | 2002 | BDNF, analog of CNTF | Guinea pig | -Deafened, AP | -Mini-osmotic pump -Scala Tympani |
-Post-deafening -26 day infusion |
-SGN: Increased SGN survival rate after treatment with BDNF and CNTF analog -ABR: Decrease in eABR threshold with BDNF + CTNF analog treatment |
| Gillespie et al. | 2003 | BDNF | Guinea pig | -Deafened, untreated -Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -4 week infusion |
-SGN: Increased SGN survival rate with continued therapy; 2 weeks following cessation of treatment led to decrease in SGN survival rates |
| Nakaizumi et al. | 2004 | CNTF, BDNF | Guinea pig | — Deafened, untreated -Normal hearing |
-Viral vector (AV) -Scala Tympani |
-Post-deafening -4 week casette expression |
-SGN: Increased SGN survival rate after treatment with BDNF or BDNF + CNTF (CTNF did not significantly enhance protective effect of BDNF) |
| Yamagata et al. | 2004 | CTNF, BDNF | Guinea pig | -Deafened, empty vector | -Mini-osmotic pump -Scala Tympani |
-Post-deafening* -2 week infusion *Neurotrop hin treatment initiated 2 or 6 weeks following deafening |
-SGN: Increased SGN density -ABR: Decreased eABR threshold starting 7 days into treatment; Significant decrease in eABR threshold 14 days after BDNF treatment; eABR threshold for treated ears after 6 week delay is significantly higher than after 2 week delay |
| Shepherd et al. | 2005 | BDNF | Guinea pig | -Deafened AP -Deafened electrode implant |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -4 week infusion |
-SGN: Increased SGN survival rate; Electrical stimulation enhances protective effects of BDNF, but produces no significant trophic support alone -ABR: Significant decrease in eABR threshold with BDNF treatment |
| Wise et al. | 2005 | BDNF, NT3 | Guinea pig | -Deafened untreated* -Normal hearing *5 or 33 days post-deafening |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening* -4 week infusion *Neurotrop hin treatment initiated 5 or 33 days following deafening |
-SGN: Increased SGN survival rate in ear 5 or 33 days after ototoxin exposure with BDNF or NT3 treatment -PAF: Variable regrowth of peripheral processes with BDNF or NT3 |
| Rejali et al. | 2007 | BDNF | Guinea pig | -Deafened, electrode + empty vector transfected fibroblast | -Viral vector (AV) treated fibroblast implant | -Post-deafening -48 days casette expression |
-SGN: Increased SGN survival rate in basal turn adjacent to coated electrode |
| Miller et al. | 2007 | BDNF, FGF | Guinea pig | -Deafened, AP + guinea pig serum albumin -Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening* -26 day infusion *Neurotrop hin treatment initiated 4 days, 3 or 6 weeks following deafening |
-SGN: Increased SGN survival rate regardless of treatment delays, but longer delay led to decreased overall SGN density -PAF: Re-growth of peripheral processes with either neurotrophin, decreased fiber re-growth with increased treatment delay |
| Agterberg et al. | 2008 | BDNF | Guinea pig | -Deafened, untreated -Normal hearing, PBS-Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -4 week infusion |
-SGN: Increased SGN survival rate and density; SGNs in treated ears are larger than normal-hearing control ears -PAF: Surrounded by thinner myelin sheath compared to normal hearing ears -ABR: No change in aABR response |
| Chikar et al. | 2008 | BDNF | Guinea pig | -Deafened, electrode implant + empty vector | -Viral vector (AV) -Scala Tympani |
-Post-deafening -80 day expression |
-SGN: Increased SGN survival rate -ABR: Decrease in eABR threshold; Correlation of eABR threshold and SGN density; No significant correlation between SGN density and psychophysical detection thresholds |
| Agterberg et al. | 2009 | BDNF | Guinea pig | -Deafened untreated -Normal hearing |
-Mini-osmotic pump -Scala Tympani |
-Post-deafening -4 week infusion |
-SGN: Increased SGN survival rate; Preserved SGN shape -ABR: eABR response comparable to normal-hearing control, and did not decrease significantly after cessation of treatment; eABR latency in treated ears are comparable to deafened control animal |
| Wise et al. | 2010 | BDNF, NT3 | Guinea pig | -Deafened untreated -Normal hearing, vector-GFP |
-Viral vector (AV) -Scala Tympani or Scala Media |
-Post-deafening -3 week expression |
Inoculation into scala media produced gene expression better localized to organ of Corti than into scala tympani -SGN: Increased SGN survival rate and -PAF: Re-growth of peripheral processes in basal turn |
| Shibata et al. | 2010 | BDNF | Guinea pig | -Deafened untreated -Deafened, empty vector (AV) |
-Viral vector (AV or AAV) -Scala Tympani |
-Post-deafening -14 or 30 day expression |
-SGN: Increased SGN survival rate -PAF: Re-growth of peripheral processes beyond the habenula perforate towards BDNF expressing cells; Insignificant decline in number of peripheral process between 14 and 30 days post-inoculation |
| Havenith et al. | 2011 | BDNF | Guinea pig | -Deafened untreated -Deafened, gelfoam + PBS -Normal hearing -Normal hearing, gelfoam + PBS |
-Neurotrophin soaked gelfoam on intact round window membrane | -Post-deafening -4 week exposure |
-SGN: Increased SGN survival rate in basal turn; No significant effect on SGN shape and size -ABR: No significant effect on eABR peak-to-peak amplitudes |
aABR--acoustically evoked auditory brainstem response; AAV—adeno-associated virus; AP—artificial perilymph; AV—adenovirus; BDNF--brain derived neurotrophic factor; CNTF--ciliary neurotrophic factor; eABR--electrically evoked auditory brainstem response; FGF--fibroblast growth factor; HSV-1—Herpes simplex virus-1; IHC--inner hair cell; NGF--nerve growth factor; NTF—neurotrophin factor; NT3--neurotrophin-3; OHC--outer hair cell; SGN--spiral ganglion neuron; PAF—peripheral auditory fiber; AP—artificial perilymph; GFP—green fluorescent protein; PBS—phosphate buffered saline