1.Losartan Prevents Maladaptive Auditory-Somatosensory Plasticity After Hearing Loss via Transforming Growth Factor-β Signaling Suppression
Seog Kyun MUN ; Kyu Hee HAN ; Jong Tae BAEK ; Suk Won AHN ; Hyun Sang CHO ; Mun Young CHANG
Clinical and Experimental Otorhinolaryngology 2019;12(1):33-39
OBJECTIVES: Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-β signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. METHODS: The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. RESULTS: Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. CONCLUSION: Losartan might prevent axonal sprouting after hearing loss by blocking TGF-β signaling thereby preventing maladaptive auditory-somatosensory plasticity.
Animals
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Axons
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Blotting, Western
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Brain Stem
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Cochlea
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Cochlear Nucleus
;
Evoked Potentials, Auditory, Brain Stem
;
GAP-43 Protein
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Hearing Loss
;
Hearing
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Losartan
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Plastics
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Rats
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Tinnitus
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Transforming Growth Factors
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Vesicular Glutamate Transport Protein 1
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Vesicular Glutamate Transport Protein 2
2.A Case of Auditory Neuropathy Caused by Pontine Hemorrhage in an Adult.
Seung Hyun CHUNG ; Sung Wook JEONG ; Lee Suk KIM
Journal of Audiology & Otology 2017;21(2):107-111
A pontine hemorrhage can evoke several neurological symptoms because the pons contains various nuclei and nerve fibers. Hearing loss can develop as a result of a pontine hemorrhage because there is an auditory conduction pathway in the cochlear nucleus of the pons. However, very few cases of hearing loss caused by pontine lesions have been reported, and there have been no reports of auditory neuropathy that developed following a pontine hemorrhage. Recently we had a patient who experienced a nontraumatic pontine hemorrhage who was diagnosed with auditory neuropathy. The 34-year-old male patient was admitted to the emergency department with sudden alteration of mental status. His brain computed tomographic imaging revealed a hemorrhage in the central pons. He complained of hearing difficulties after his mental status recovered through conservative treatment, but a pure-tone audiogram showed very mild hearing loss in both ears. Further hearing tests using otoacoustic emissions, which showed normal responses, and auditory brainstem responses, which showed no waveforms at maximum stimulus intensity, revealed that his hearing difficulties were caused by auditory neuropathy. This case implies that the threshold of sound detection can be preserved in patients with pontine hemorrhage who complain of hearing difficulties. Auditory neuropathy should be considered as a possible cause of hearing difficulties in these patients and appropriate hearing tests should be performed.
Adult*
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Brain
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Cochlear Nucleus
;
Ear
;
Emergency Service, Hospital
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Evoked Potentials, Auditory, Brain Stem
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Hearing
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Hearing Loss
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Hearing Loss, Central
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Hearing Tests
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Hemorrhage*
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Humans
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Male
;
Nerve Fibers
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Pons
3.Changes of response patterns to excitatory stimuli of different intensities: a model-based study of cochlear nucleus neurons.
Jiahao LIU ; Chao WANG ; Zhongju XIAO ; Linghong ZHOU
Journal of Southern Medical University 2014;34(3):291-294
OBJECTIVEThe cochlear nucleus (CN) neurons show 3 principal response patterns to short tone bursts, namely the primary-like, chopper and onset response patterns. We previously established an excitatory model to simulate the response patterns of CN neurons to stimuli. In this study, we aimed to investigate the effects of excitatory intensity on the CN neuron response patterns and explore the role of inhibitory inputs under normal physiological conditions.
METHODSBased on the platform of Matlab and the excitatory model derived from the integrate-and-fire model, we altered the intensity of excitatory inputs in dB range and obtained the histograms to analyze the changes in the response patterns of the neurons using OriginPro 7.5 data analysis software.
RESULTSThe original primary-like response pattern of the neurons did not vary significantly while the chopper and onset response patterns changed into primary-like responses with the increase of the excitatory input intensity. But this response pattern alteration as a result of excitatory input intensity changes was rarely observed under normal physiological conditions.
CONCLUSIONSThe CN neurons receive balanced excitatory and inhibitory inputs, which stabilize the neuronal membrane potential within a limited range. The balanced inhibitory inputs decide the response pattern of a given neuron.
Acoustic Stimulation ; Cochlear Nucleus ; physiology ; Evoked Potentials, Auditory ; Models, Neurological ; Neurons ; physiology
4.Functional refinement of bushy cells in the anterior ventral cochlear nucleus precedes hearing onset in neonatal rats.
Shenghui ZHONG ; Zhenggang ZHANG ; Mingyu FU ; Juan YANG ; Zhongju XIAO
Journal of Southern Medical University 2014;34(7):923-927
OBJECTIVETo investigate the development of the electrophysiological property of bushy cells in the anterior ventral cochlear nucleus (AVCN) of neonatal Sprague Dawley (SD) rats.
METHODSThe development of action potential and spontaneous miniature excitatory postsynaptic currents (mEPSCs) in AVCN bushy cells were investigated by whole-cell patch-clamp technique in SD rats during the postnatal days 5-21 (P5-21). The half band width of the action potential (AP), 10%-90% risetime and decay tau of the mEPSCs were analyzed.
RESULTSThe AP of the bushy cells became faster with age from P5 to P21 and stopped changing around the period of hearing onset, as evidenced by the alteration of half band width of the AP. The time accuracy of mEPSCs of the bushy cells also increased with age and stabilized around hearing onset as shown by briefer 10%-90% rise time and decay tau of mEPSCs in P14/P21 than in P7.
CONCLUSIONThe functional refinement of the bushy cells in the AVCN precedes hearing onset in neonatal rats.
Action Potentials ; Animals ; Cochlear Nucleus ; cytology ; Excitatory Postsynaptic Potentials ; Hearing ; Neurons ; cytology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Synapses
5.Compare NRT value of straight electrode and contour electrode in Nucleus 24 cochlear implant system.
Yong TAO ; Yun ZHENG ; Kai WANG ; Zhaoli MENG ; Ke XU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(1):8-10
OBJECTIVE:
To learn the neural response of spiral ganglion cell to electrical stimulus by comparing the neural response telemetry(NRT) value between straight electrode and contour electrode in Nucleus 24 cochlear implant system.
METHOD:
Fourty-six patients with Nucleus 24 cochlear implants were paired into two groups: 23 with contour electrode and 23 with straight electrode respectively. NRT value of each group were tested and compared.
RESULT:
The NRT value of straight electrode fell in the range of 160 microV to 170 microV and contour electrode 150 microV to 160 microV. The NRT were going up higher a little bit from electrode twenty to electrode one.
CONCLUSION
The contour electrode requires less power consumption than straight electrode in Nucleus 24 cochlear implant system.
Action Potentials
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Child
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Child, Preschool
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Cochlear Implantation
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Cochlear Implants
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Cochlear Nucleus
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Electrodes
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Female
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Humans
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Infant
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Male
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Telemetry
6.Response properties of cochlear nucleus neurons: a digital model-based study.
Yue-jin XU ; Ling-hong ZHOU ; Zhong-ju XIAO
Journal of Southern Medical University 2011;31(1):77-81
OBJECTIVETo investigate the mechanisms of different response patterns of the cochlear nucleus neurons based on a digital model.
METHODSBased on the platform of Matlab7.0 and the integrate-and-fire model, we constructed the temporal coding model.
RESULTSThe model well simulated the response types of the primary-like, chopper, onset and buildup neurons by changing the settings of some parameters related to the properties of the neurons.
CONCLUSIONSThe properties of the neurons dictate the response patterns of the cochlear nucleus neurons. The simulation results are consistent with the literature. Understanding of the response properties of the cochlear nucleus neurons can provide assistance in the study of the auditory system.
Cochlear Nucleus ; physiology ; Computer Simulation ; Humans ; Models, Neurological ; Neurons ; physiology
7.NMDAR expression in the cochlear nucleus and hearing damage in neonatal rats with hyperbilirubinemia.
Ke-Fang LI ; Kai-Xian DU ; Yue-Xing JIANG ; Xue-Lei DONG ; Yan ZHANG
Chinese Journal of Contemporary Pediatrics 2010;12(3):201-204
OBJECTIVETo study the role of N-methyl-D-aspartate-receptor (NMDAR) expression in the development of hearing damage in neonatal rats with hyperbilirubinemia.
METHODSSixty seven-day-old Sprague-Dawley rats were randomly injected with bilirubin of 100 microg/g (low-dose treatment group) or 200 microg/g (high-dose treatment group) or normal saline (control group). Auditory brainstem response (ABR) was examined. The concentrations of bilirubin in blood and brain were measured. NMDAR expression in the cochlear nucleus slices was examined by immunohistochemistry assay.
RESULTSABR reflecting threshold obviously increased, and I, II and III wave latency as well as I-II, II-III and I-III interval were more prolonged in the two bilirubin treatment groups when compared with the control group. The NMDAR expression in the cochlear nucleuse in the two bilirubin treatment groups was obviously lower than that in the control group. The NMDAR expression in the cochlear nucleuse was negatively correlated with the brain bilirubin content and the ABR reflecting threshold in the two bilirubin treatment groups.
CONCLUSIONSAn increased NMDAR activity may play an important role in hearing damage following hyperbilirubinemia.
Animals ; Animals, Newborn ; Bilirubin ; analysis ; Cochlear Nucleus ; chemistry ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Disorders ; etiology ; Hyperbilirubinemia ; complications ; metabolism ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis
8.Tinnitus: Characteristics, Causes, Mechanisms, and Treatments.
Byung In HAN ; Ho Won LEE ; Tae You KIM ; Jun Seong LIM ; Kyoung Sik SHIN
Journal of Clinical Neurology 2009;5(1):11-19
Tinnitus-the perception of sound in the absence of an actual external sound-represents a symptom of an underlying condition rather than a single disease. Several theories have been proposed to explain the mechanisms underlying tinnitus. Tinnitus generators are theoretically located in the auditory pathway, and such generators and various mechanisms occurring in the peripheral auditory system have been explained in terms of spontaneous otoacoustic emissions, edge theory, and discordant theory. Those present in the central auditory system have been explained in terms of the dorsal cochlear nucleus, the auditory plasticity theory, the crosstalk theory, the somatosensory system, and the limbic and autonomic nervous systems. Treatments for tinnitus include pharmacotherapy, cognitive and behavioral therapy, sound therapy, music therapy, tinnitus retraining therapy, massage and stretching, and electrical suppression. This paper reviews the characteristics, causes, mechanisms, and treatments of tinnitus.
Auditory Pathways
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Autonomic Nervous System
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Cochlear Nucleus
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Massage
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Music Therapy
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Otoacoustic Emissions, Spontaneous
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Tinnitus
9.Immunoreactivity of Calcium-Binding Proteins in the Central Auditory Nervous System of Aged Rats.
Seok Min HONG ; Seung Young CHUNG ; Moon Sun PARK ; Young Buhm HUH ; Moon Suh PARK ; Seung Gun YEO
Journal of Korean Neurosurgical Society 2009;45(4):231-235
OBJECTIVE: While many factors contribute to aging, changes in calcium homeostasis and calcium related neuronal processes are likely to be important. High intracellular calcium is toxic to cells and alterations in calcium homeostasis are associated with changes in calcium-binding proteins, which confine free Ca2+. We therefore assayed the expression of the calcium binding proteins calretinin and calbindin in the central auditory nervous system of rats. METHODS: Using antibodies to calretinin and calbindin, we assayed their expression in the cochlear nucleus, superior olivary nucleus, inferior colliculus, medial geniculate body and auditory cortex of young (4 months old) and aged (24 months old) rats. RESULTS: Calretinin and calbindin staining intensity in neurons of the cochlear nucleus was significantly higher in aged than in young rats (p<0.05) The number and staining intensity of calretinin-positive neurons in the inferior colliculus, and of calbindin-positive neurons in the superior olivary nucleus were greater in aged than in young rats (p<0.05). CONCLUSION: These results suggest that auditory processing is altered during aging, which may be due to increased intracellular Ca2+ concentration, consequently leading to increased immunoreactivity toward calcium-binding proteins.
Aged
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Aging
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Animals
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Antibodies
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Auditory Cortex
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Auditory Pathways
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Calcium
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Calcium-Binding Protein, Vitamin D-Dependent
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Calcium-Binding Proteins
;
Cochlear Nucleus
;
Geniculate Bodies
;
Homeostasis
;
Humans
;
Inferior Colliculi
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Nervous System
;
Neurons
;
Olivary Nucleus
;
Rats
10.Electrical Cellular Physiology in Cochlear Nucleus Using Patch-Clamp Techniques.
Korean Journal of Otolaryngology - Head and Neck Surgery 2009;52(6):474-481
No abstract available.
Cochlear Nucleus
;
Patch-Clamp Techniques

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