前庭器官的胚胎发育及前庭中枢的髓鞘形成.pdf

E mb r y o l o g i c a I D e v e l o p me n t o f V e s t i b u l a r 0 My e l i n a t i o n o f P o s t n a t a I C e n t r a I V e s t i b u l a r 前庭器官的胚胎发育及前庭中枢的髓鞘形成 Ki mit ak a Kag a Ch en c hieh Ku a n a n d m 近年对眩晕疾病的关注程度越来越高 但多集中于临床 诊疗技术而对基础研究的关注稍显不足 为此我们特邀原日 本东京大学加我君孝教授撰写了关于 前庭系统胚胎发育和 前庭 中枢髓鞘形成 的文章 作者根据多年的临床经验和研 究并在参考相关文献基础上完成此稿 本文虽是关于基础研 究的文章但却具有较强的实用性 对指导临床思维具有一定 帮助 为使广大读者能更好的理解作者思想 现将全文予以 刊登同时做导读一篇供大家参考 伴有半规管功能下降的听力障碍 儿童在出生后的前2 N3 年会出现粗大运动与平衡功能的发育延缓 此后患儿的多数 粗大动作如头部控制 独自直立 行走和奔跑等都可以随着 年龄的增长得到进一步发育 然而 在进入学龄期6 岁左右其 平衡功能仍存在不同程度的问题 情况比较好的患儿可以游 泳 而较差的则只能在睁眼情况下保持静态平衡 尽管所有 儿童都可以具有 良好的运动能力 但这是由于前庭 中枢代偿 的结果 是基于视觉 躯体感觉和本体感觉等其他感觉传人信 号的整合以及出生后小脑运动控制系统和运动皮层的成熟共同 协调完成的 前庭中枢代偿在帮助先天性前庭功能下降的婴儿 或儿童发展运动能力上起着重要作用 因此为了更好的理解前 庭中枢代偿过程 有必要了解前庭外周器官的胚胎发育以及前 庭中枢系统的髓鞘形成过程 作者分章节详细介绍了前庭 外周器官 如椭圆囊 球 囊 半规管的胚胎发育过程以及前庭神经节 前庭 中枢系统 的发育特点 重点介绍了神经发育过程 中的髓鞘形成及相关 研究 相对于成人前庭神经节细胞的组织病理学研究而言 胎儿和新生 L 婴儿的前庭神经节组织学细胞病理学研究很 少 在对人胚胎颞骨连续切片的研究中 追踪了从第1 3 周到第 3 9 周胎龄的前庭神经节细胞的形态改变 发现在妊娠第2 4 周时 前庭神经节细胞已成熟 但直到第3 9 周细胞质体积仍在持续增 加 同时 本文详细地阐述了髓鞘在神经冲动传导和轴突发育 中的重要作用 髓鞘的形成是神经发育的最后一步 亦是决定 功能发育的主要形态学参数 作者在文章中还引用了许多经典 的研究成果 F l e c h s i g 1 9 0 1 首次提出中枢神经系统的髓鞘形成程度可能与其功 能相 关 他的贡献 1 9 2 0 在于完成了一套新生儿 早产 儿 足月产儿以及出生早期婴儿的脑切片 参见原文图7 其髓鞘形成理论遵循由后 向前 从低到高 由内向外的顺序 发育完善 首先是传入神经髓鞘发育 感觉 其次为传出 神经 运动 最后是联合神经纤维 的髓鞘发育 第八对 颅神经是首批形成髓鞘的神经之一 Y a k o v l e v a n d L e c o u r s 1 9 6 7 提出了髓鞘周期理论 参见原文图8 他们认为 胚胎期 的髓鞘形成开始于周围神经系统 此后 中枢神经系 统开始 形成髓 鞘 感 觉系统 的髓鞘形 成先 于中枢运 动系 统 而大脑 半球 内的髓鞘形成出生后才开 始并可持续数十 年 尤其 是涉及更 高级联合功能和感觉辨 别区域的纤维髓 鞘发育较晚 作者通过对脑核磁前庭中枢系统的研究发现 虽出生前 的脑干部分已具备髓鞘形成 但与颞骨组织切片的研究结果 相比 中枢前庭系统的发育是滞后于前庭终末器官发育的 即前庭终末器官在胚胎发育早期即发育成熟 而 中枢前庭系 统在出生后还在发育成熟中 直到1 N2 岁时其中枢髓鞘发育 才逐渐达到成人水平 因此至学龄前随着生长发育和 中枢代 偿的作用 所有儿童大部分的粗大运动都可以得到良好的发 育 通过对前庭神经系统发育过程的研究 使我们更好的了 解了前庭系统的中枢代偿作用至关重要 而前庭 中枢代偿对 加速婴儿及儿童发育的运动功能具有重要的临床价值 刘博张娜 首都医科大学附属北京同仁医院 北京市耳鼻咽喉科研究所 K i mi t a k a K a g a 加我君孝 原 日本东 京大学附属病院耳鼻 咽喉科主任教授 国际医学教育研究 中心 主任 现 E l 本东京 医疗 中心感觉器研 究所所 长 E l 本著名耳科学专 家 在人工耳蜗植人手术 人工听觉脑干植入手术 全中耳再建手术及外耳成形术等基础与临床研究方面具有较突出的贡献 在 听觉诱发 电 位 听觉 中枢皮层 婴幼儿平衡发育 颧骨病理组织学 新生儿听力筛查 脑与言语发育 脑与音乐等研究领域也颇 有造诣 已发表相 关论 文1 0 0 余篇 著书1 0 余部 主持 日本文部省和厚生省重大课题近1 0 项 246 I中 国医 学 文摘耳 鼻 咽喉 科 学 N E WS AN D RE V i E WS S e p t e mb e r 2 0 0 8 Vo 1 2 3 No 5 维普资讯 1 nt r oduct i on De v el o p me n t o f g r o s s mo t o r b al a n c e a n d l o c o mo t i v e f u n c t i o n wa s s e r io u s l y d e l a y e d i n d e a f in f a n t s a n d c h i l d r e n wi t h l os s of se mi c i r c ular c an al f un c t ion du r i n g t h e fir s t 2 or 3 y ea r s o f l i f e Ther ea f t er al l c hil dr e n c ou l d ac hi e ve mos t l an dmar k s o f gr o ss mo t or d ev el opment s uc h a s h ead c on t r ol i n depe nden t st an di n g wal ki ng an d r unni ng un t i l sch ool age Ho wev er ba l an ce f u nc t ions ev en at t he age o f ent r a nc e of t h e element ar y s c h o o l 6 一 y e a r o ld w e r e v a r i o u s l y i mp a i r e d i n e a c h c a s e a n d t h e be er c as e c ould s wim un de r wat er bu t t h e poo r ca se c ou l d n ol mai nt ai n s t a t i c bal anc e wi t h e yes closed but wi t h ey es ope n Alt h ou gh fin e mot or s k i l l s we r e nor mal l y ac hi e ve d in al l c a s es t he se g r os s mot or de velopmen t due t o c ent r al v es t i bu l ar c o mpen sa t i on c oul d d epen d on t h e i nt egr at ion of i n pu t s f r Om t he o t he r sen s ory i np ut s su c h as v i s ual s oma t os ens or y and p r opr i oc ept i v e s ens es and t he po s t na t al ma t ur a t i on of mo t or c o n t r o l s y s t e ms i n t h e c e r e b e l l u m b a s a l g a n g l i a a n d mo t o r c o r t ex I3 4 Cent r al v es t i bul ar com p ensat i on coul d p l a y i mpor t ant r ol es t o ac c el er a t e dev el opmen t al mo t or f un c t i ons of i nf ant s an d c hi l dr en i n s pi t e of c onge ni t al l os s of v es t i bul ar or gans For under st andi ng t h e c en t r al ves t i bul ar c ompens at i on t he embr yologi c al de velopmen t of ve st i bul ar end or g ans and t he po s t n at al my el i n at i on of cen t r al v e s t i bu l ar s y s t e m i s d es cr i be d he r e 2 Em br yol ogi cal devel opm ent of vest i bul ar or gans 2 1 ut r cl e an d sa cuul e A s mal I d epr es sion de ve l op s be t we en t h e sa c cu l e and c oc hl e ar du c t By t h e e nd of t h e 7 t h week it is a de ep c on s t r ic t i on f or mi na t he duc t u s r eun i en s Du e t o t h e d eep eni n g of t he 3 f olds i n t h e au di t ory ves i c l e al t he en d of t he 8t h week t he en dol y mphat i c du c t s ac cu l e an d u t r icle s ho w ch ar ac t e r i s cs o f t h ei r a dult f or m A V s hap ed du cl j s f o r med whi c h c o mmuni c at e s be t ween t he u t r icle and t he s ac uu l e an d is c omp os ed o f t h e s ac cu l o end ol y mph at ic d uc t on o n e s i d e a n d t h e u t r ic u l o e n d o l y mp h a t ic d u c t o n t h e o t h e r T h e e n d o ly mp h a t i c d u c t i s j o in e d wit h t h e b a s e o f t h e V g i v i n g it a Y s h ape d app ea r an c e I n I at er s t ages t he f i r s t au dit or y f ol d f or ms t he ut r i c ul o en dolymp h at ic valv e Thi s v alve is a f o l d a t t he o pening of t h e u t r i c ul ar d uc t i n t o t he u t r i c l e Th e f u nc t i o n of t hi s v al v e i s n ot wel I un der s t ood Ther e ar e s o me i ndic at ions t h a t t h i s v alve ma y clos e o ff t h e u t r i c ular du c t C e ll s o f t h e n e u r o e p it h e li u m s e c r e t e the o t o lit h ic me mb r a n e o f th e ma c u la e F i g 1 a n d the c u p u l a e o f th e c r i s t a e a s s m a l l d r o p l e t s o f a gela t in ou s s ub s t an c e wh i c h r u n t og e t h er Rh ombic c r y s t a l s o f c a l c iu m c a r b o n a t e C a C 03 a r e f o u n d a s o t o c o n ia in t h e g e la U n o u s s u bs t an c e o f t h e o t o l i t hi c membr a ne Dur i n g t he 1 1 t h week t h e d iff er en t ia t ion o f t h e s en s o r y an d s up p ort i n g c ell s is c o mp l e t e d a n d the r es u lU n g ma c u l a e are s i mi lar t o t ha t o f t h e a du K 1 1 2 w e e k ma c u la P e a r s o n e t a l 1 9 7 0 2 2 De vel opment of semi ci r cul a r duct s Dur ing t h e 6 t h week t he s emi c i r cul ar du c t s d evelop as 2 e vagi na t i on s or f l a t t end o u t p o c k e t i n g s f r 0 m t h e u t r i c u l a r p a r t d o r s a l a u d i t o ry v e s i c l e of t he membr an ous l ab yr i n t h The wall s o f t he v er t i c al pa rt o f t h e d or s a I v e s t i b u l a r o u t p o c k e t i n g a d h e r e t o e a c h o t h e r i n t wo p l aces Thes e ar e as of adher ence wi l I be come f oc i f or a b s o r p t i o n T h e e p it h e l i u m j 1 3 t h e s e a d h e r e d p l a c e s j s d e s t r o y e d or p us he d a wa y b y t h e i n gr o wt h of mes en ch y me The r es ult is t h e f o r mat i on of t he 3 s em The f i r st r egi on wher e t hi s OC CU r s i s i n t he a r ea of t he f ut u r e supe r i o r sem i ci r cuI a r d uc t t he s ec on d i s i n t he r e g i o n o f t h e p os t er i o r c ir c u l a r d u c t s F ig 2 m m ac uI a e an d c r i s t ae 1 9 7 0 罔 c o n t a i n i n g s e n s o r y h a i r c e l l s F i g 3 a n d s u p p o r t i n g c e l l s di ffer en t i a t e in t he epit hel i um o ver l y i ng t he a r eas wh er e t he 中 国 医学 文摘 耳鼻 咽 喉 科学 NE WS A ND RE VI E WS S e p t e mb e r 2 0 0 8 V o 1 2 3 N o 5 I R47 维普资讯 ner vefiber s enter T he epithel iumwi l Im odifysomewhatinto a pseudost r ati fiedlayerbeforer each ingitsadultstr uctur e Thedi latedendsofthe3semicir cularducts ar ecal led ampul lae The ampul latedends ofthe superior andtheIater aI ducts openclosetoeachothe rintotheupperendofthe utricule andtheampul latedendofthe post eriorductopens intotheIow er endoft he sac T he non am pul l atedendsofthe post eriorandsuperiorductsfusetoforma common stemcal led the cruscom m une whichopensintothemi ddle partofthe utricle The post erior non ampul lated endoft helater al due opensindependentl yInt ot heutricle ThetotaInumberofcrura t hatent erthe utricleisf ive InFi gure 4 tempor albonehistologyofvestibular end organs atthe13thw eekand18thweekofgestationalagein fetuses ar eshow n Jtjsclearthatvesti bularendorganscan differ entiateMeryearl ierr atherthan cochlear F i g 4 Semicir cular canals andotol ithicorgans atthe13thweekoffeutus a Cochlearduct Cor t i s organdoesnotappearbutonl y pri m i t ivebasic layeris ob se r ved b Semicir cularcanalandthe saccules 10 wm agnif ication c Ampul laandsensorycel lslayer ofthehorizontalsemicircularcanal d 0toconiaandotol ithm embrane ofm acul la saccul i Atmi d t e r m maxim um gr owthi sdevelopedbythe superior semicir cularduc t Atthe sametim e theendol ymphati cductis beingbentanddir ectedcaudadalongitslongaxi s T he post eriorandthentheIater aIsemicircularductr each their maxim um grow th Ther efor e theducts continueto gr ow andr eachtheir m axim umsizeinthesam e ordertheywere established superior post eriorandlater aI Nowthe entire m embr anouslabyrint hhasreachedits adultsize 3Embryologic aldev elo pm entof ve st ibular gangli o n s T henor malhistologyofvesti bul arganglion cel lsinthe fetus andthepatholog yofvest ibulargangl ioncel l sin neonates andinfants ar e r arel yst udied in contrasttothehisOpath010aicaI stud ies ofvesti bulargangl ion cel lsin adults Vestibul argangl ion cel ls areuni quelyl ocated jnthe vesti bular nerve asthefir st order n euronsinthe nar row and deepinter nalaudi torycanal Because oftheuni que anatomicaIIocations ofvestibul ar gangl i on cel lsbetween t hebrain andlabyrinth pathol ogical reactions speci fictothesecells can occur In ourpaper ther esults ofanor m alstudyofvestibular gangl i onsinthefetusandpathol ogicalstudieson vestibular gangl i on cel lsinpediatriccasesinthetemporalbone serial sect ions ar e studied In our study wetr acedthem OrphOIOgicaIchangesin vesti bularganglion cellsinhum anfetuses rangingfrOm13th w eeksto39thw eeks ofgestationalagebyusing13temporal boneserialsections Vestibulargangl ioncel lshadreached histologicalm aturi t ybythe 24thweekofgestationandthe volum e ofvestibulargangl ion cel lcytoplasmincr easedunt ilt he 39thw eekofgestation F i g 5show s morphologicalchanges ofvestibularganglion cellsinhum anfetuses rangingfrO mthe13t hw eektot he 39thweekofgestationalage Vesti bulargangl ion cel ls r each histologicalm aturi t ybythe 24thw eekofgestation andthe volum elncrease untiltheb irt h Fi g 5 Embryologicalchanges ofvesti bularganglions S ca rpa s gangl i on aComparisonofvestibulargangl ionswit h developm entT hesizeof vesti bulargangl ionsincr easewi t hembryiologicalage b C hanges ofsquar e ofvesti bulargangl ionswithdevelopmnt 4Developme ntofce ntralve sti bular syste m 4 1Neu r odevelopm entand M yel i nstructur e During developm ent thecentralner voussystem istr ansform ed f rOmathinlayer ofundi fferentiated t issueintoacomplex m ulti layer edsystem thatis capable ofpr ocessinginfor m ation a ndo rganizingactio ns Them ajor eve ntsincentr aI ner vous systemdevelopm entinclude prim aryneur ulation pr osencephaIi cdevelopm ent neur onalandgl ialpr oli feration neuronalmi gr ati on axonoutgr owth dendritic gr owthand synapsefo r m ation andmyel ination Tabl el M yel i nat ion isthelaststepoftheneuraldevelopm entandis oneoft he promi nentm orphologicalparam eter sfordeter miningfunctional development Table1Majoreventsin ner ual developm ent Prim ar yncurulation Pr osencephal ic cleavage ventralindcution Neur onaIpr ol i fera t i on Cerebr al Cerebellar Neur onaImi gr ation Cer ebr aI Cerebel lar Neur onaldifier entiation Axonoutgr owth Dendriticgr owt handsynapsefor m a t i on Synaptic r earr angem ent M yel ina t i on 3 4 wk 5 6wk 2 4m o 2 10m o postnat al 3 5 m o 4 10m o postnat aI 3m o b i rth 6mo 1yrpostnatal B irthyeam post natal B irth yeampostnat al 248 l中国医学文摘耳鼻咽喉 科学NE WSA N DR E V IE WS September2008 V01 23 No 5 维普资讯 4 2M yel inStr uctu re Themyelin sheathis anextended m odif ledPIasm am embr a net hatisw r aPpedi nasPIr aI fashion aroundaportionofanaxon Eachmyel insheathis composedofmultiple segm ents ofmyeli n whichar e modified extensionsofOIigOdendr OgIiaIcel lprocesses Further more eachol i godendrocyt ecancontri butemyel intoas manyas50 dif fer entaxonsT he sections ofmyelinar e separ atedfr O m each otherbysinailsegm entsIn whichthebar e axoni sexposedto theinter stitiaIspace T hese segm ents callednodesofRanvier ar etheIocat ion ofm ultiplesodiumchannels Whenthe axon membr aneisexcited thegeneratedelectricalimpulsecannot f lowthroughthehi gh r esistancemyel insheat h Hence it flow s outanddepolarizesthe axonalm embr aneatthenext node whichmightbe1m morfartheraw ayfr omit T heIow capacitanceofthesheathal lowsthedeD Olarizationofthe r emainingmembr anebet weent henodesconsistingl it tleenerg y andm arkedl yi ncr easedspeed In ad dit iontoitsimportance inner veimpulseconduction myelinmayhave asymbiotic r elationshipwiththeaxon Evi dencehasalsobeenpubl ished suggestingt hatmyel inissynergistic withthedevelopingaxon andthattheaxonaIcytoskeletondoes notfor mproperlyinthe absence ofmyel in Fi g 6 F ig 6 Schem aticdiagram showingacross sectionofa mYeIinatedaxon Notehow themyelin wh ich derivesfr O m exte nsionoface Ipr ocess frO man Ol i gOdendr O cyt e w r aps ar oundthe axon m ulti pl e t i mesto f or ma spiral 4 3M yel i nat ionstudybyPaulF lechsi g F lechsi g 1901 w astheori gi nator ofholdingtheviewthatthedegreeof myel inationoftheCNSmi ghtbe cor r elatedwith functional capacity Inhistheory hestartedthatmyel inationstartedin pr oj ectionpat hwaysbefore associationpathwayswhereasin peripher alner ves ar ebefor ecentr al T houghhedidmodify h istheorysli ghtlybecause ofh is cri t ics thestatem entwher e fiber s alw aysmyel inateinthe same orderr em ainedthesam e fir sttheaffer ent sensor y thentheef fer ent m otor t henthe associat ionfi ber s F lechsi g 1901 pr epar eda setofbrai n sectionsf r o mthehum an newbor n pr emature f ul l t er m and earl y postnatali nfants Fi g 7 Hediscoveredthataxonsin differ entpartsr eceivetheir myel in sheathatdifferentstages ofgr owth and he coul dobserv ethechr onologicalsequence 0fthis pr ocess T her esearcher outIinedthesequenceof myel inationpr ocess f rOmtheposteriorparttothe anteriorpart fr omthelowerpart tothe up perpart fromm ediaItoIater al He alsopointedout thatmyel inationisthepr ominentmorphological par am etersf ordeterminingfunctionaIdevelopm ent T heV III ner veisamongthefir sttocontaint he myel inatedf i ber s The statoacousticnucleusandpathwayare consi der edt odevelop myel inationinthefetalandearlypostnatalperi ods 4 4Yakovlev and Leco ur s w o rk m myel in cycle Yakovlev and Lecour s 1967 pr ovi dedthe m ostinfor mat i vedescri pt ions ofthe myelinationpr ogressinhum anbr ains Byusingt he Loyezmethodforstainingmyel in t heydefinedthedevelopm ent ofmyel inin25ar easofthehunl anner v ous system 朋 1 F q l Fetus34cm 髟 Fetus34cm Gestation8m onth Post na tal9m ortth F i g 7 F lechsi g 1920 outl i nedthe sequenceofmyel inationpr ocess fr omthe post enorparttothe anteriorpart fr omthelowerparttothe up perpart 仃Om mediaItoIater al T hedata provi dedimportantinfor mationandsever al gener alpoi ntsw er emade First myel inationbeginsinthe peripheraIner voussystem wherem otorroots myel i natebefor e sensor y r oots Second shortl ythereaf terandsti lIbeforebirth myelin appear sintheCNSinthebr ainstemandcerebel lum Thefir ststructur estomyel inatear ecompo nents ofsom e major sensor y systems e g m ediallemniscusfor som esthetic stim uli 1ater aI Iem niscus trapezoi dbody and br ach ium oft he inferior col l iculusforauditor y stim ul ilandcomponents ofsom e m ajorm otor system s e g corticospinaltr actinthe midbr ain andponsandsuperior cer ebel larpeduncle In contr astto t he peripheralner voussystem system stendstopr ecedethat myel inat ionin centr alsensor y ncentralmotorsystem Third myel inat ionwithint hecer ebraIhemispher es particularl yt hose r egionsjnvolvedjnhigherJeveJassociativefunctions and sensor y discriminations e g association ar eas intracortical neur opil andcer ebr aIcommissur es starts wel Iaf terb irthand progresses overdecades Yakovlev and Lecours 1967 also poi ntedoutthatthefi br e syst emsinthebrainstemm ed iat ing vesti bularandacousticm odal ities ofexperience e g m edial longitudinalbundle laterallem niscus myel i nate earl yi nthe hum anfetalstageanddevelopr apidl ybef orebirth Figur e8 i IIustr atesYakovlev s myelincyclein1964 wh ichshow sthebeginningandendingofmyel inationineach 中国医学文摘耳鼻咽喉科学N EWSAN D R E V IE WS September2008 V01 23 No 5 24日 静卜 髻J 一习 维普资讯 neur onalpat hway T h is alsoi l lustratest hatmyel incyclesd i f fer in eachneur onalpathw ayinbr ain Eachneuronalpathw ayin r edcoloris r elatedto centr alvesti bularpathway YakovlevandLec ours F i g 8 Yakovlev s myelincyclef 1964 M yel i n cyclesdi fferineachneur onal pathwayi nbr ain Eachneuronalpathw ayin r edcolorisrelated to centr al vestibularpathway 4 5Vesti bularpathways Vesti bularpathwaysrunfrO mthe ei ghthner ve andthe vesti bul arnucleithr 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