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Effects of chronic furosemide on central neural hyperactivity and cochlear thresholds after cochlear trauma in Guinea pig.

Mulders WH, McMahen C, Robertson D - Front Neurol (2014)

Bottom Line: The activity of single IC neurons was recorded 24 h following the last injection.The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus.These results that suggest a long-term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

View Article: PubMed Central - PubMed

Affiliation: The Auditory Laboratory, School of Anatomy, Physiology and Human Biology, The University of Western Australia , Crawley, WA , Australia.

ABSTRACT
Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously, we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioral evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper, we measured the effects of a chronic (daily injections for 7 days) furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10-kHz, 124 dB, 2 h acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80 mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 h following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long-term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

No MeSH data available.


Related in: MedlinePlus

(A) Mean threshold loss (mean ± SEM) at multiple frequencies after recovery from acoustic trauma (day 12) from animals that were treated with saline (open circles, n = 4) of furosemide (black circles, n = 5). (B) Histogram showing median spontaneous firing rate in CNIC in saline (362 neurons from four animals, white bar) and furosemide treated groups (398 neurons from five animals, black bar) 12 days after acoustic trauma. Median shown with 25 and 75% percentile. (C) Histogram showing median spontaneous firing rate of CNIC neurons in high and low frequency regions in saline treated animals (white bars) and furosemide treated animals (black bars) on day 12 after acoustic trauma. Bars show median with 25 and 75% percentile **p < 0.01; ****p < 0.0001.
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Figure 1: (A) Mean threshold loss (mean ± SEM) at multiple frequencies after recovery from acoustic trauma (day 12) from animals that were treated with saline (open circles, n = 4) of furosemide (black circles, n = 5). (B) Histogram showing median spontaneous firing rate in CNIC in saline (362 neurons from four animals, white bar) and furosemide treated groups (398 neurons from five animals, black bar) 12 days after acoustic trauma. Median shown with 25 and 75% percentile. (C) Histogram showing median spontaneous firing rate of CNIC neurons in high and low frequency regions in saline treated animals (white bars) and furosemide treated animals (black bars) on day 12 after acoustic trauma. Bars show median with 25 and 75% percentile **p < 0.01; ****p < 0.0001.

Mentions: Figure 1A shows the average CAP threshold loss in the exposed ear of both saline and furosemide treated animals on day 12 after the acoustic trauma. Both groups of animals showed CAP threshold losses at frequencies >10 kHz in line with data published previously using the same animal model (5, 16). Furthermore, there were no statistically significant differences between the groups at any frequency, including the lower frequencies that were unaffected by the acoustic trauma. These results show that the chronic administration of furosemide did not have additional lasting effects on the peripheral thresholds.


Effects of chronic furosemide on central neural hyperactivity and cochlear thresholds after cochlear trauma in Guinea pig.

Mulders WH, McMahen C, Robertson D - Front Neurol (2014)

(A) Mean threshold loss (mean ± SEM) at multiple frequencies after recovery from acoustic trauma (day 12) from animals that were treated with saline (open circles, n = 4) of furosemide (black circles, n = 5). (B) Histogram showing median spontaneous firing rate in CNIC in saline (362 neurons from four animals, white bar) and furosemide treated groups (398 neurons from five animals, black bar) 12 days after acoustic trauma. Median shown with 25 and 75% percentile. (C) Histogram showing median spontaneous firing rate of CNIC neurons in high and low frequency regions in saline treated animals (white bars) and furosemide treated animals (black bars) on day 12 after acoustic trauma. Bars show median with 25 and 75% percentile **p < 0.01; ****p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126040&req=5

Figure 1: (A) Mean threshold loss (mean ± SEM) at multiple frequencies after recovery from acoustic trauma (day 12) from animals that were treated with saline (open circles, n = 4) of furosemide (black circles, n = 5). (B) Histogram showing median spontaneous firing rate in CNIC in saline (362 neurons from four animals, white bar) and furosemide treated groups (398 neurons from five animals, black bar) 12 days after acoustic trauma. Median shown with 25 and 75% percentile. (C) Histogram showing median spontaneous firing rate of CNIC neurons in high and low frequency regions in saline treated animals (white bars) and furosemide treated animals (black bars) on day 12 after acoustic trauma. Bars show median with 25 and 75% percentile **p < 0.01; ****p < 0.0001.
Mentions: Figure 1A shows the average CAP threshold loss in the exposed ear of both saline and furosemide treated animals on day 12 after the acoustic trauma. Both groups of animals showed CAP threshold losses at frequencies >10 kHz in line with data published previously using the same animal model (5, 16). Furthermore, there were no statistically significant differences between the groups at any frequency, including the lower frequencies that were unaffected by the acoustic trauma. These results show that the chronic administration of furosemide did not have additional lasting effects on the peripheral thresholds.

Bottom Line: The activity of single IC neurons was recorded 24 h following the last injection.The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus.These results that suggest a long-term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

View Article: PubMed Central - PubMed

Affiliation: The Auditory Laboratory, School of Anatomy, Physiology and Human Biology, The University of Western Australia , Crawley, WA , Australia.

ABSTRACT
Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously, we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioral evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper, we measured the effects of a chronic (daily injections for 7 days) furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10-kHz, 124 dB, 2 h acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80 mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 h following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long-term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

No MeSH data available.


Related in: MedlinePlus