噪声及水杨酸钠引起下丘及皮层的电活动改变

发布时间：2018-02-08 22:36

本文关键词： 耳鸣侧抑制电生理下丘听觉皮层　出处：《中国人民解放军医学院》2013年博士论文　论文类型：学位论文

【摘要】：背景耳鸣为无相应的外界声源或电刺激，而主观存在的声音感觉。耳鸣的发生率约为3%-30%，约有l%-3%的人群因耳鸣而影响正常生活和工作。一些能导致听力损失(噪声暴露、老龄化、药物、外伤)的原因均可能引起神经性耳鸣。排除一些器质性病变而引起的耳鸣外，常见的神经性耳鸣多为主观性的。由于神经性耳鸣的客观评定方法局限，定位诊断困难，为临床治疗难题。耳鸣的发生机制尚不清楚，一般认为，中枢听觉系统(CAS)的抑制性神经作用减弱，引起中枢神经电活动改变是耳鸣形成的神经生理基础。中枢听觉系统神经电活动改变可能是源于耳蜗损伤，引起包括听觉皮层(AC)、下丘(IC)和耳蜗核(CN)等中枢听觉系统，某些区域的抑制功能下调。耳鸣机制的研究应建立可靠的耳鸣动物模型,采用行为学或电生理学方法，结合耳鸣的临床特征进行研究。本文利用噪声暴露和大剂量水杨酸钠（SS）建立动物模型，采用电生理学方法记录、分析和量化，对下丘和听觉皮层的改变进行分类和评估。方法与结果第一部分用C57小鼠作为噪声暴露模型，16导微电极记录噪声暴露前后下丘神经的神经电活动反应情况。放电活动结果包括频率反应域和放电频率-声音强度函数，频率反应域结果表明某些下丘神经的特征性频率(CF)在噪声暴露前后由高频区域转变到低频区域，某些神经的最小阈值在噪声暴露后升高；而某些神经的最佳频率和最小阈值有明显升高；某些神经没有发生明显改变。放电频率-声音强度函数表明某些低频神经在噪声暴露后放电频率会增加，而高频神经在噪声暴露后放电频率会降低。比较噪声暴露前后的Q10值，在噪声暴露后调谐曲线的形状变宽，所记录的下丘神经自发性放电活动比暴露前减弱。第二部分（1）用成年Sprague Dawley（SD）大鼠作为动物模型，16导微电极记录大剂量SS注射前后听觉皮层神经的放电活动变化。腹部注射大剂量SS后3小时内听觉皮层放电活动递增。（2）用成年SD大鼠,16导微电极记录,分别研究药物GABA类似物和钾离子通道开放剂对大剂量SS引起的听觉皮层高放电活动所产生的影响。分别测试了GABA类似物组、GABA类似物+SS组、钾离子通道开放剂组、钾离子通道开放剂+SS组。药物注射5分钟后注射水杨酸钠，GABA类似物+SS组和钾离子通道开放剂+SS组的放电率增加的幅度会低于水杨酸钠注射组。这表明GABA类似物和钾离子通道开放剂可部分抑制水杨酸钠引起的听觉皮层高放电活动。结论（1）噪声暴露可能引起下丘中枢侧抑制的损伤，这些抑制性区域一般存在于比下丘神经的特征性频率（CF）较低的频率区域，CF迁移和调谐曲线变宽主要发生在高于噪声暴露频率的神经区域，噪声暴露后下丘神经自发性放电即刻降低，，这不同于噪声暴露一段时间后自发性放电的改变。上述电活动改变表明噪声暴露后耳蜗接受到的传入神经信号减少，影响正常的听觉传导通路，下丘神经的可塑性变化可能是引起耳鸣的原因，并解释了噪声引起的耳鸣频率范围与噪声的频率有关，即耳鸣的频率常低于噪声暴露频率。（2）大剂量水杨酸钠可以引起听觉皮层放电频率增高，GABA类似物和钾离子通道开放剂可以降低听觉皮层的放电频率，这两种药物对大剂量水杨酸钠对听觉皮层的电生理功能均有影响。GABA类似物和钾离子通道开放剂可能对耳鸣有抑制作用。上述研究会帮助我们进一步认识耳鸣的发生机制，对于耳鸣治疗也提供了线索。
[Abstract]:background
Tinnitus without corresponding external sound source or electrical stimulation, and the sound of subjective feeling. The incidence of 3%-30% is about tinnitus, about l%-3% of the population because of tinnitus and affect the normal life and work. Some can cause hearing loss (noise exposure, aging, drugs, trauma) causes are likely to cause nerve tinnitus. Some organic lesions caused by tinnitus, nervous tinnitus is common. Due to the limitations of subjective objective evaluation methods of nervous tinnitus, positioning diagnostic difficulties for clinical treatment problems.
The mechanism of tinnitus is unclear, is generally believed that the central auditory system (CAS). The inhibitory nerve function, caused by the electrical activity of CNS neural and physiological basis of tinnitus change is formed. The electrical activity of auditory CNS changes may be due to the induced cochlear injury, including auditory cortex, inferior colliculus (IC (AC)) and cochlear nucleus (CN) and the central auditory system, inhibit the function of certain areas down. Mechanism of tinnitus research should establish a reliable animal model of tinnitus, using behavioral or electrophysiological methods, combined with the clinical characteristics of tinnitus in research.
The animal models were established by noise exposure and high-dose sodium salicylate (SS). The changes in the inferior colliculus and auditory cortex were classified and evaluated by electrophysiological methods.
Methods and results
Part one
Using C57 mice as a model of noise exposure, 16 by neural activity reaction were recorded before and after noise exposure. The inferior colliculus neuron discharge activity including frequency response area and discharge frequency - sound intensity function, frequency response characteristic frequency domain results show that some IC nerve (CF) in the high frequency region after noise exposure to low frequency area, the minimum threshold of certain nerves increased in noise exposure; and the optimum frequency of certain nerves and minimum threshold increased significantly; some nerve showed no change. The discharge frequency of sound intensity function shows that some low frequency noise exposure in nerve discharge frequency will increase, while the high frequency noise exposure in nerve discharge frequency will be reduced. Comparison of the Q10 values before and after noise exposure, the noise exposure tuning curve shape becomes wide, spontaneous discharge recorded neural activity in inferior colliculus than Abate before exposure.
The second part
(1) Adult Sprague Dawley (SD) rats were used as animal models, and 16 guided microelectrodes recorded the changes of nerve activity in auditory cortex before and after high-dose SS injection. After 3 hours of abdominal injection, the activity of auditory cortex increased.
(2) with adult SD rats, 16 channel microelectrode recording, respectively studies the influence drug GABA analogues and potassium channel openers on high dose SS induced auditory cortex produced high discharge activity. Tested the GABA analogue group, GABA analogue group +SS, potassium channel opener group. Potassium channel opener +SS group. Drug injection 5 minutes after injection of sodium salicylate, discharge GABA analogue group +SS and potassium channel opener +SS group the rate of increase is lower than sodium salicylate injection group. This indicated that GABA analogues and potassium channel openers can inhibit sodium salicylate induced auditory cortex high discharge activity.
conclusion
(1) may cause central lateral inhibition injury of inferior colliculus noise exposure, these inhibitory regions generally exist in the ratio of characteristic frequency inferior colliculus (CF) nerve in the lower frequency region, CF migration and wide tuning curve occurs mainly in the neural region is higher than the frequency of noise exposure, inferior colliculus neuron spontaneous discharge of immediate reduction in noise exposure after the noise exposure is different from the change of spontaneous discharge after a period of time. The change shows that the electrical activity of afferent signal after noise exposure to reduce the influence of the cochlea, auditory pathway normal, plasticity of hypothalamic nerve may cause tinnitus, and explain the noise induced tinnitus frequency range and noise the frequency, the frequency of tinnitus is often less than the frequency of noise exposure.
(2) a large dose of sodium salicylate can cause the auditory cortex increased the discharge frequency, discharge frequency of GABA analogues and potassium channel openers can reduce the auditory cortex, these two kinds of drugs on a large dose of sodium salicylate on the auditory cortex electrical physiological function of both.GABA analogues and potassium channel openers may have an inhibitory effect on the tinnitus.
The above research will help us to further understand the mechanism of tinnitus and provide clues for the treatment of tinnitus.

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R764.45

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