Reversible neurotoxicity of kanamycin on dorsal cochlear nucleus

Fan, Guoxin; Yin, Zedeng; Sun, Yu; Chen, Sen; Zhang, Wenjuan; Huang, Xiang; Kong, Weijia; Zhang, Honglian

doi:10.1016/j.brainres.2012.12.049

Cited by 7 publications

(7 citation statements)

References 77 publications

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“…At this time, we are left with paradoxical and unexplained finding that KM is neurotoxic to postnatal SGN and ANF whereas gentamicin is not. Some clues regarding its neurotoxic potential may be gleaned from a recent study showing that KM caused considerable mitochondrial swelling, vacuole formation and endoplasmic reticulum dilation in adult dorsal cochlear nucleus neurons; however, these effects were largely reversible (Fan et al, 2013). Further work is needed to more fully elucidate the mechanism underlying KM neurotoxicity in P3 SGN and ANF.…”

Section: Discussionmentioning

confidence: 99%

“…After systemic streptomycin injection, an acute neurotoxic effect rapidly occurs to the cochlear afferent and efferent terminals prior to the hair cell degeneration; this significantly increased the latency of the compound action potential and wave I and the interwave intervals of the auditory brains stem response 20 min after streptomycin treatment (Ding and Salvi, 2005, Ding et al, 2010b). Some studies also suggest that kanamycin (KM) exerts neurotoxic effects on neurons in the dorsal cochlear nucleus (Fan et al, 2013). In cases where gentamicin was infused into the cochlear, a noticeable loss of SGN occurred in the first week post-treatment; this was followed by an even greater loss of SGN over the next 30 weeks (Dodson and Mohuiddin, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

et al. 2017

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Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed towards the apex in a dose dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3 mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

et al. 2017

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“…[43], [44] Neurons were counted only if their nuclei were completely within the margins of the visual system by using Image-Pro-Plus (6.0) software (Media Cybernetics, Inc., USA). All images were acquired using the same exposure time and illumination conditions.…”

Section: Methodsmentioning

confidence: 99%

Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

Zhou

Zhang

et al. 2013

PLoS ONE

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Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN) and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3) in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL). Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.

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“…The transgene has a role in stress resistance in CNS Aminoglycoside is known to be toxic not only to the cochlea but also to the central auditory system. 42,43 We analyzed the neuron morphology by Nissl staining and TEM and also determined the stress level, as indicated by the expression of GRP78, between subgroups and found that the PGC-1α transgene decreased the stress level, which indirectly confirms the existence of viral vectors in the CNS after cochlear inoculation.…”

Section: Detection Of Viral Particles In Cns By Temmentioning

confidence: 87%

“…Animal brains were embedded in paraffin according to the process of Fan et al 42 The slides were serially sectioned at 5 μm thickness in the coronal direction at the level of the AC and CN by consulting the atlas of the rat brain for the basic orientation. 70 One out of every eight sections was selected for analysis from all the serial sections in our study.…”

Section: Immunofluorescence/immunohistochemistrymentioning

confidence: 99%

The spread of adenoviral vectors to central nervous system through pathway of cochlea in mimetic aging and young rats

Chen

Zhao

et al. 2015

Gene Ther

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There is no definitive conclusion concerning the spread of viral vectors to the brain after a cochlear inoculation. In addition, some studies have reported different distribution profiles of viral vectors in the central auditory system after a cochlear inoculation. Thus, rats were grouped into either a mimetic aging group or a young group and transfected with adenoviral vectors (AdVs) by round window membrane injection. The distribution of AdV in central nervous system (CNS) was demonstrated in the two groups with transmission electron microscopy and immunofluorescence. We found that the AdV could disseminate into the CNS and that the neuronal damage and stress-induced GRP78 expression were reduced after transfection with PGC-1α, as compared with the control vectors, especially in the mimetic aging group. We also found that the host immune response was degraded in CNS in the mimetic aging group after transduction through the cochlea, as compared with the young group. These results demonstrate that viral vectors can disseminate into the CNS through the cochlea. Moreover, mimetic aging induced by D-galactose could facilitate the spread of viral vectors into the CNS from the cochlea. These findings may indicate a new potential approach for gene therapy against age-related diseases in the CNS.

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Reversible neurotoxicity of kanamycin on dorsal cochlear nucleus

Cited by 7 publications

References 77 publications

Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

The spread of adenoviral vectors to central nervous system through pathway of cochlea in mimetic aging and young rats

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