动物生理学原理耳鸣和听觉过敏的神经生物学机制ppt课件.ppt
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1、Advances in neurobiology of tinnitus and hyreracusis耳鸣和听觉过敏的神经生物学研究进展杨明建2014.12.16研究背景研究背景Hearing impairment is a considerable disease burden.It hasbeen estimated that adult-onset hearing impairment is the thirdleading cause of disability (WHO,2008).Forty-two previous reports published between 1973
2、and 2010 in 29 countries have revealed increased hearing loss with age;Developing countries report higher rates of moderate and moderately-severe hearing impairment due to higher rates of pre-and postnatal childhood infections such as rubella(风疹)风疹),measles(麻(麻疹)疹)and meningit(脑膜炎)(脑膜炎),and from the
3、 use of ototoxic drugs(耳毒性药物)(耳毒性药物)(Stevens et al.,2013).However,in industrialized countries,noise-induced hearing loss (NIHL)(噪声性听力损失)(噪声性听力损失)is a common cause of hearing impairments (Lu et al.,2005),with a prevalence that is second to presbycusis(老年性耳(老年性耳 聋)聋)(Stanbury et al.,2008).Hyperacusi a
4、nd tinnitus are potentially devastating conditions that are still incurable.Epidemiology(流行病学)(流行病学)of tinnitusTinnitus is a disorder of perception of phantom sound that is also known as ringing in the ear or head.Tinnitus affects 1020%of the general population (Galazyuk et al.,2012;Shargorodsky et
5、al.,2010);According to the American Tinnitus Association,an estimated 50 million people in the United States have chronic tinnitus,persisting for longer than six months (Shargorodsky et al.,2010).For 12 million individuals,it is severe enough to interfere with daily activities.Tinnitus can occur in
6、children (Shetye and Kennedy,2010)and prevalence increases with age (Adams et al.,1999;Ahmad and Seidman,2004),peaking between 60 and 69 years of age(Shargorodsky et al.,2010).More common in men than in women,more likely in former smokers,and in adults with hypertension,hearing impairment,loud noise
7、 exposure,or generalized anxiety disorder(广泛性广泛性焦虑障碍)焦虑障碍)(Shargorodsky et al.,2010).Hearing loss and stress (emotional as well as psychosocial)are important risk factors for tinnitus (Hebert et al.,2012;Jastreboff,2007;Langguth et al.,2009),although tinnitus can occur independently from broad incre
8、ase of hearing thresholds (Geven et al.,2011;Langers et al.,2012;Lockwood et al.,2002).耳鸣的分类耳鸣的分类耳鸣有耳鸣有间歇性,也有持续性间歇性,也有持续性。有。有单一频率窄带噪单一频率窄带噪音或白噪音音或白噪音等多种表现。耳鸣一般可分为等多种表现。耳鸣一般可分为中枢性中枢性及周围性两大类及周围性两大类。周围性耳鸣根据是否被别人听。周围性耳鸣根据是否被别人听见分为见分为主观性耳鸣和客观性耳鸣主观性耳鸣和客观性耳鸣。前者多见,后。前者多见,后者少见。耳鸣又可根据其特征分为者少见。耳鸣又可根据其特征分为持续性耳鸣
9、与持续性耳鸣与节律性耳鸣节律性耳鸣。持续性耳鸣可有单一频率或多频率。持续性耳鸣可有单一频率或多频率声调的混合,多为主观性耳鸣。节律性耳鸣多与声调的混合,多为主观性耳鸣。节律性耳鸣多与血管跳动一致,偶尔与呼吸一致,耳鸣的频率较血管跳动一致,偶尔与呼吸一致,耳鸣的频率较低。如为肌肉收缩引起,则耳鸣的频率较高。节低。如为肌肉收缩引起,则耳鸣的频率较高。节律性耳鸣,多为客观性耳鸣。律性耳鸣,多为客观性耳鸣。Epidemiology(流行病学)(流行病学)of hyperacusisHyperacusis is a disorder of loudness perception(响度感知紊乱)(响度感知
10、紊乱),in which sound intensities that are considered comfortable by most people are perceived unbearably loud (Baguley,2003).In hyperacusis,sounds are not simply a bit loud,but truly unbearable(难以忍受)(难以忍受).Hyperacusis can occur without a loss of hearing thresholds (Gu et al.,2010).Statistics on hypera
11、cusis are scarce,and although it is often coincident with tinnitus,limited evidence has supported the co-occurrence of the two conditions (Andersson et al.,2002;Gu et al.,2010;Nelson and Chen,2004).With an approximate prevalence of about 1015%of the population (Gilles et al.,2012),the prevalence of
12、hyperacusis is comparable to tinnitus (Shargorodsky et al.,2010).For tinnitus and hyperacusis,hearing loss,however,is a major risk factor.As the incidence of hearing loss will increase with the aging of the population,also the incidence of tinnitus and hyperacusis may increase.Are tinnitus and hyper
13、acusis in the ear or the brain?越来越多的证据表明耳鸣和听觉过敏形成的机制中越来越多的证据表明耳鸣和听觉过敏形成的机制中外周听觉器官损伤只是起因外周听觉器官损伤只是起因,耳鸣和听觉过敏的形,耳鸣和听觉过敏的形成和维持更多的是成和维持更多的是 听觉传导通路上各级中枢的作听觉传导通路上各级中枢的作用用。耳蜗损伤耳蜗损伤等造成的异常神经活动经中枢核团逐等造成的异常神经活动经中枢核团逐级传递并在边缘系统等非听觉系统的参与下最终在级传递并在边缘系统等非听觉系统的参与下最终在听皮层被感知为耳鸣。听皮层被感知为耳鸣。M.Knipper,P.V.Dijk,I.Nunes,et a
14、l.Advances in the neurobiology of hearing disorders:Recent developments regarding the basis of tinnitus and hyperacusis Progress in Neurobiology,111 (2013)1733J.J.Eggermont,L.E.Roberts.The neuroscience of tinnitus.TRENDS in Neurosciences,27(2004)676-682.Fig.1.Schematic illustration of the adult orga
15、n of Corti.The nerve fibers of IHCs(内毛细胞)send information to the brain,whereas the nerves of OHCs(外毛细胞)mainly receive information from the brain.IHCs are,therefore,the true sensory cells of hearing.OHCs are characterized by their electromotile properties;they are responsible for the amplification of
16、 the acoustic signal,which in turn activates IHCs.The IHCs transmit electrical signals in a frequency-specific manner to higher auditory brain areas.内耳柯蒂氏器(螺旋器)示意图1.cochlear damageNIHL(噪声性听力损失)(噪声性听力损失)has been,in a previous view,typically defined by a permanent loss of hearing thresholds(听阈永久性损失)(听
17、阈永久性损失).Normal thresholds rely on the proper function of outer hair cells (OHCs)(Dallos and Harris,1978).Per inner ear,there are approximately 11,000 OHCs,which are,in the human cochlea,typically arranged in 3 rows (Fig.1,OHC).OHC function is to nonlinearly amplify basilar membrane vibration in resp
18、onse to soft sounds near the place of characteristic frequency within the cochlea (Ashmore,2008).OHCs are therefore crucial for the high sensitivity of the hearing organ,its frequency selectivity,and understanding speech in noise (Ashmore,2008;Dallos,2008).After mild acoustic overexposure,hearing fu
19、nction can recover within 23 weeks (Miller et al.,1963).This corresponds to a temporary threshold shift(暂时性阈移)(暂时性阈移)due to reversible damage to the mechanosensory hair bundles of hair cells (Fig.1,stereocilia)(Liberman and Dodds,1984a,b;Schneider et al.,2002).After intense or repeated acoustic over
20、stimulation,however,hearing function stabilizes at an elevated value,leading to permanent threshold shift(永久性阈移)(永久性阈移)that mostly occurs due to destruction of OHCs(Spoendlin,1985).In the daily clinical routine,permanent hearing loss is typically detected through the increase of hearing thresholds a
21、s tested by tone-audiometry(听力测定)(听力测定).More detailed clinical diagnostic testing may also include auditory brainstem response (ABR)(听性脑干反应)(听性脑干反应)testing or recording distortion product otoacoustic emissions (DPOAEs)(畸变产物耳声发射)(畸变产物耳声发射).ABR responses represent the summed activity of neurons in the
22、 ascending auditory pathways.The specific function of intact OHCs can be measured by amplitudes of DPOAEs.DPOAEs are acoustic signals that arise from distortions in the OHCs mechanoelectrical response to two continuous tones.These distortion products,which are at frequencies not present in the input
23、 stimulus,are generated by the OHCs biological motors and can be detected with a microphone in the ear canal.DPOAEs responses thus reflect the electromotile properties of OHCs (Fitzgerald et al.,1993;Huang et al.,2005).We can conclude that loss of hearing thresholds after noise exposure is mostly li
24、nked to OHC loss,which specifically can be measured by DPOAEs.Through DPOAE and ABR measurements,in combination,a differential damage of OHCs and IHCs can be detected.Fig.2.Predicted subcellular positions of high-and low-SR fibers at the inner haircell (IHC).Afferent auditory nerve fibers of IHCs ar
25、e classified accordingto their spontaneous action potential discharge rate (SR).High-threshold,low-and medium-SR fibers are presumably preferentially located at the modiolar side of the IHC,where larger ribbons are associated with smaller patches of NMDA-R and AMPA-R.Low-threshold,high-SR fibers are
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