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Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs.

Agterberg MJ, Versnel H, van Dijk LM, de Groot JC, Klis SF - J. Assoc. Res. Otolaryngol. (2009)

Bottom Line: The amplitude of the suprathreshold eABR response in BDNF-treated animals was significantly larger than in deafened control animals and comparable to that in normal-hearing control animals.The amplitude in the BDNF-treated group did not decrease significantly after cessation of treatment.The eABR latency in BDNF-treated animals was longer than normal and comparable to that in deafened control animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, GA, Utrecht, The Netherlands.

ABSTRACT
Exogenous delivery of neurotrophic factors into the cochlea of deafened animals rescues spiral ganglion cells (SGCs) from degeneration. To be clinically relevant for human cochlear implant candidates, the protective effect of neurotrophins should persist after cessation of treatment and the treated SGCs should remain functional. In this study, the survival and functionality of SGCs were investigated after temporary treatment with brain-derived neurotrophic factor (BDNF). Guinea pigs in the experimental group were deafened, and 2 weeks later, the right cochleae were implanted with an electrode array and drug delivery cannula. BDNF was administered to the implanted cochleae during a 4-week period via a mini-osmotic pump. After completion of the treatment, the osmotic pumps were removed. Two weeks later, the animals were killed and the survival of SGCs was analyzed. To monitor the functionality of the auditory nerve, electrically evoked auditory brainstem responses (eABRs) were recorded in awake animals throughout the experiment. BDNF treatment resulted in enhanced survival of SGCs 2 weeks after cessation of the treatment and prevented the decreases in size and circularity that are seen in the untreated contralateral cochleae. The amplitude of the suprathreshold eABR response in BDNF-treated animals was significantly larger than in deafened control animals and comparable to that in normal-hearing control animals. The amplitude in the BDNF-treated group did not decrease significantly after cessation of treatment. The eABR latency in BDNF-treated animals was longer than normal and comparable to that in deafened control animals. These morphological and functional findings demonstrate that neurotrophic intervention had a lasting effect, which is promising for future clinical application of neurotrophic factors in implanted human cochleae.

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Related in: MedlinePlus

Recordings of representative eABRs evoked with current pulses of 400 μA down to below threshold in two control animals (gp-sp02 and gp-ju02) and one experimental animal (gp-mr02). Recordings of two control animals are depicted to illustrate the inter-animal variability. A, C Recorded in normal-hearing condition, prior to deafening; B, D recorded 5 and 6 weeks after deafening, respectively. E Recorded after 4 weeks of BDNF treatment and F 2 weeks after cessation of the treatment. T indicates the threshold of wave N1–P2. The arrow indicates the peak that probably reflects the digastric muscle response.
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Fig7: Recordings of representative eABRs evoked with current pulses of 400 μA down to below threshold in two control animals (gp-sp02 and gp-ju02) and one experimental animal (gp-mr02). Recordings of two control animals are depicted to illustrate the inter-animal variability. A, C Recorded in normal-hearing condition, prior to deafening; B, D recorded 5 and 6 weeks after deafening, respectively. E Recorded after 4 weeks of BDNF treatment and F 2 weeks after cessation of the treatment. T indicates the threshold of wave N1–P2. The arrow indicates the peak that probably reflects the digastric muscle response.

Mentions: Figure 7 shows eABR recordings in two animals (top and middle row) in the normal (A, C) and deafened (B, D) condition. The decrease in N1–P2 amplitude after deafening was prominent in the recordings after deafening for current levels of 318 and 400 μA. The thresholds in these examples did not change after deafening. The P3 of the eABR recordings in gp-sp02 (A, B) at stimulus intensities of 400 and 318 μA was influenced by the digastric muscle response (arrow). Figure 7E, F depicts eABR recordings in gp-mr02 after 4 weeks of BDNF treatment (i.e., 6 weeks after deafening) and 2 weeks after cessation of BDNF treatment (i.e., 8 weeks after deafening). The N1–P2 amplitude did not decrease after cessation of BDNF treatment, and the threshold did not change.FIG. 7


Enhanced survival of spiral ganglion cells after cessation of treatment with brain-derived neurotrophic factor in deafened guinea pigs.

Agterberg MJ, Versnel H, van Dijk LM, de Groot JC, Klis SF - J. Assoc. Res. Otolaryngol. (2009)

Recordings of representative eABRs evoked with current pulses of 400 μA down to below threshold in two control animals (gp-sp02 and gp-ju02) and one experimental animal (gp-mr02). Recordings of two control animals are depicted to illustrate the inter-animal variability. A, C Recorded in normal-hearing condition, prior to deafening; B, D recorded 5 and 6 weeks after deafening, respectively. E Recorded after 4 weeks of BDNF treatment and F 2 weeks after cessation of the treatment. T indicates the threshold of wave N1–P2. The arrow indicates the peak that probably reflects the digastric muscle response.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2717388&req=5

Fig7: Recordings of representative eABRs evoked with current pulses of 400 μA down to below threshold in two control animals (gp-sp02 and gp-ju02) and one experimental animal (gp-mr02). Recordings of two control animals are depicted to illustrate the inter-animal variability. A, C Recorded in normal-hearing condition, prior to deafening; B, D recorded 5 and 6 weeks after deafening, respectively. E Recorded after 4 weeks of BDNF treatment and F 2 weeks after cessation of the treatment. T indicates the threshold of wave N1–P2. The arrow indicates the peak that probably reflects the digastric muscle response.
Mentions: Figure 7 shows eABR recordings in two animals (top and middle row) in the normal (A, C) and deafened (B, D) condition. The decrease in N1–P2 amplitude after deafening was prominent in the recordings after deafening for current levels of 318 and 400 μA. The thresholds in these examples did not change after deafening. The P3 of the eABR recordings in gp-sp02 (A, B) at stimulus intensities of 400 and 318 μA was influenced by the digastric muscle response (arrow). Figure 7E, F depicts eABR recordings in gp-mr02 after 4 weeks of BDNF treatment (i.e., 6 weeks after deafening) and 2 weeks after cessation of BDNF treatment (i.e., 8 weeks after deafening). The N1–P2 amplitude did not decrease after cessation of BDNF treatment, and the threshold did not change.FIG. 7

Bottom Line: The amplitude of the suprathreshold eABR response in BDNF-treated animals was significantly larger than in deafened control animals and comparable to that in normal-hearing control animals.The amplitude in the BDNF-treated group did not decrease significantly after cessation of treatment.The eABR latency in BDNF-treated animals was longer than normal and comparable to that in deafened control animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, GA, Utrecht, The Netherlands.

ABSTRACT
Exogenous delivery of neurotrophic factors into the cochlea of deafened animals rescues spiral ganglion cells (SGCs) from degeneration. To be clinically relevant for human cochlear implant candidates, the protective effect of neurotrophins should persist after cessation of treatment and the treated SGCs should remain functional. In this study, the survival and functionality of SGCs were investigated after temporary treatment with brain-derived neurotrophic factor (BDNF). Guinea pigs in the experimental group were deafened, and 2 weeks later, the right cochleae were implanted with an electrode array and drug delivery cannula. BDNF was administered to the implanted cochleae during a 4-week period via a mini-osmotic pump. After completion of the treatment, the osmotic pumps were removed. Two weeks later, the animals were killed and the survival of SGCs was analyzed. To monitor the functionality of the auditory nerve, electrically evoked auditory brainstem responses (eABRs) were recorded in awake animals throughout the experiment. BDNF treatment resulted in enhanced survival of SGCs 2 weeks after cessation of the treatment and prevented the decreases in size and circularity that are seen in the untreated contralateral cochleae. The amplitude of the suprathreshold eABR response in BDNF-treated animals was significantly larger than in deafened control animals and comparable to that in normal-hearing control animals. The amplitude in the BDNF-treated group did not decrease significantly after cessation of treatment. The eABR latency in BDNF-treated animals was longer than normal and comparable to that in deafened control animals. These morphological and functional findings demonstrate that neurotrophic intervention had a lasting effect, which is promising for future clinical application of neurotrophic factors in implanted human cochleae.

Show MeSH
Related in: MedlinePlus