前庭代偿动物模型方法综述北大核心CSCD

前庭疾病是耳鼻喉科的一种常见疾病,常在前庭系统发生病变或受到非生理性刺激时出现,患者可出现平衡失调、眼球震颤、眩晕等前庭功能障碍以及恶心、呕吐、面色苍白、心悸等自主神经系统功能异常的表现,严重影响了患者的生活质量。虽然这些症状在人或动物身上都可通过前庭代偿机制在数周或数月得到改善,但代偿的时间和最终的恢复水平都有极大的个体差异,所以研究前庭代偿的机制对提高前庭疾病的治疗效果意义重大。由于临床伦理的诸多限制,建立相应动物模型成为了研究前庭代偿机制的重要手段。目前的建模方式主要有:手术切除、化学性迷路破坏、手术+化学方法破坏迷路及空气注射。经过各国科研工作者几十年的不懈努力,也取得了诸多可喜成果,但还远远不够。明晰前庭代偿机制并指导临床的诊疗工作仍然任重而道远,建立相似性高、重复性好的动物模型十分必要。在此综述已有模型为研究人员构建合适模型提供理论基础。     

前庭代偿的发生机制

前庭代偿是一个中枢过程,其发生机制很复杂。本文从神经生理学、神经化学及神经药理学方面进行综述,供同道参考。     

单侧前庭功能丧失患者前庭眼反射和视支反射眼震电图定量 …

OBJECTIVE: To study changes of the vestibular function in the process of vestibular compensation. METHODS: The electronystagmography recording of spontaneous nystagmus(SN) with tests for vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) were performed in 105 patients with unilateral loss of vestibular function, the results were analysed quantitatively. RESULTS: (1) Twenty-one patients with courses from 3 days to 6 years presented a SN directed towards the intact side, with an average slow phase velocity (ASPV) of 7.12-12.07 degrees/s. (2) The intensity of VOR nystagmus as a response to the warm-cold water stimulation to the intact ear was lower than that of normal subjects. (3) By 0.167 Hz, 90 degrees sinusional oscillation stimulation, the ASPVs of the patients' VOR nystagmus directed towards the intact and affected sides were lower than that of the normal. A predominance of VOR nystagmus rotation towards the intact side was found in patients with courses < or = 5 years. There was no predominance of VOR nystagmus found in patients with courses > 5 years. (4) There was no significant difference between the optokinetic nystagmus (OKN) intensity of the normal persons and that of patients with lesions outside the cerebellopontine angle and with tumors in cerebellopontine angle which was < 2.5 cm in diameter. The OKN intensity of patients with tumors in cerebellopotine angle with diameters > or = 2.5 cm was lower than that of normal subjects. A predominance of OKN towards the intactside was found in these patients. CONCLUSION: The vestibular function is in inhibitory and the vestibular system becomes rebalanced due to this inhibition in the process of vestibular compensation.     

电刺激确认前庭代偿早期前庭核神经元

目的探讨电刺激前庭神经末梢在前庭代偿早期确认具有放电可能的前庭神经元的可行性.方法电刺激迷路切除术后8小时、24小时和48小时三组动物前庭神经末梢,比较是否给予电刺激时前庭神经核神经元放电细胞个数和放电频率变化情况.结果术后8小时仅记录到一个自发性放电细胞,电刺激后细胞放电频率增加.随着代偿时间推移,当电刺激前庭神经末梢,前庭神经核中神经元放电数目和放电率增加,暂停电刺激时神经元放电率下降.结论电刺激前庭神经末梢可增强前庭代偿早期在体前庭神经元细胞放电,具体表现为神经元放电率与放电细胞的数目增加,应用该方法可在前庭代偿早期选择具有一定放电可能的前庭神经元.     

安定对前庭功能及前庭代偿影响的研究进展

本文复习安定的应用药理学，就其对前庭功能及前度代偿的影响进行综述。指出安定对前庭功能有一定的抑制作用，对前庭代偿过程可产生不同的影响，认为研究结果的差异与多种因素有关。     

前庭代偿过程中前庭传出性和传入性神经系统的相互作用

目的 通过前庭代偿的动物模型，了解在前庭病变的情况下，前庭传出性和传入性神经系统的相互作用。方法 动物模型：A组(16只)为正常大鼠。B组(15只)左侧前庭损毁术后7d。C组(7只)术后3个月。D组(7只)前庭代偿后。检测两侧头长肌静息状态的肌电图。检测传出性前庭神经系统降钙素基因相关肽免疫组化。检测传出性前庭神经系统胆硷乙酰转移酶(choline acetyltransferase，AChT)免疫组化。检测传入性前庭神经系统Na-K-ATP酶活性。结果 损伤同侧肌群肌电活动减弱、对侧肌群增强，前庭代偿期恢复对称性。急性期传出性前庭神经系统降钙素基因相关肽阳性细胞双侧性增多，活性增高。传出性前庭神经系统损伤同侧AChT阳性反应细胞减少，两侧反应程度增加。前庭代偿期对侧反应程度显著增加。急性期同侧Na-K-ATP酶mRNA表达水平低，对侧前庭信号增强，在前庭代偿期，同侧Na-K-ATP酶mRNA表达水平增强，与对侧一致或略强。结论 传出性前庭神经系统可能抑制对侧前庭传入信息，调整同侧前庭中枢兴奋性，在前庭代偿的复杂机制中发挥作用。     

前庭自发眼震对视觉平稳跟踪功能的影响

目的:探讨前庭自发性眼震（spontaneous nystagmus,SN）对视觉眼动系统平稳跟踪功能的影响。方法:对46例存在SN的急性单侧外周性前庭综合征患者（前庭神经炎26例、Ramsay-Hunt综合征伴眩晕6例、突发性聋伴眩晕14例）行视频眼震图平稳跟踪试验（smooth pursuit test,SPT）和...     

前庭代偿过程中Ⅰ组代谢性谷氨酸受体亚型在前庭内侧核中的变化

目的观察单侧迷路破坏术后前庭内侧核(medialvestibular nuclei,MVN)内I组代谢性谷氨酸受体亚型(group I metabotropic glutamate receptors,mGluR1)的表达变化。方法成年雄性Wistar大鼠28只,分为迷路破坏组(20只)和对照组(8只),前者破坏单侧迷路,对照组手术方式相同但保持迷路完好。单侧迷路破坏术后,通过免疫组织化学、原位杂交组织化学法检测不同存活时间(术后12h、36h、7d、30d)两组动物MVN内mGluR1的表达变化。结果单侧迷路破坏术后可诱导同侧MVN区I组代谢性谷氨酸受体亚型mGluR1减少,术后12h最少,术后36h开始增加,至术后7d和30d后和对照组差异无统计学意义;对侧和术侧的变化趋势相同。结论单侧迷路破坏术后可诱导MVN区I组代谢性谷氨酸受体亚型mGluR1减少。初级前庭传入或中枢前庭神经元的静息放电降低可能与I组代谢性谷氨酸受体亚型mGluR1减少有关,但其在前庭代偿中的作用尚有待研究。     

Effect of diazepam on vestibular compensation in squirrel monkeys

Summary The effect of the chronic administration of diazepam on vestibular compensation (post-unilateral labyrinthectomy) was studied in squirrel monkeys.An intramuscular injection of diazepam (2 mg/kg) was given daily for a period of 4 weeks post-operatively. After daily injection, reduction of the slow-phase eye velocity (SPEV) of spontaneous nystagmus and enhancement of locomotor body dysequilibrium were found in the early post-operative stage. However, these pharmacological effects decreased gradually and almost no remarkable effect was found about 3 weeks after surgery. When compared to control animals, no marked differences was found in SPEV reduction of spontaneous nystagmus in injected animals during the vestibular compensation period. Platform runway tests showed that the average number of calendar days needed to regain the pre-operative level of locomotor balance function in the group injected with diazepam was even less than that of the control group. Thus, post-operative daily diazepam injections did not retard the vestibular compensation. The possible neural mechanism responsible for this phenomenon is discussed.     

Optokinetic nystagmus and vestibular stimulation in squirrel monkey model

Summary Simultaneous application of the rotatory stimulus with a constant angular acceleration (1/sec²) did not clearly improve the optokinetic pursuing ability in squirrel monkeys, even though the directions of vestibular and visual stimuli matched.When the directions of vestibular stimulus and visual stimulus conflicted, the optokinetic pursuing ability markedly declined regardless of the stimulus magnitude. The inter-individual difference was large in that situation.For the vestibular-visual coordination, the active head movement condition is considered to be natural and important as a biological function.This study was supported in part by NASA Contract NAS-9-14546, and NINCDS grants: NS-10940 and NS-07237     

人胚胎期前庭水管生长发育模式分析

目的　探讨人胚胎期前庭水管生长发育特征 ,以便更好地理解前庭水管扩大的起源。方法　应用 3DMed医学图像分析软件对 6～ 3 8周 (每隔 1周 2例 )的 3 2具人胎儿颞骨连续组织病理切片进行观察分析 ,测量不同胎龄前庭水管内口、外口、中点直径和管长度 ,经曲线拟合描述其生长发育模式。结果　胚胎 6周时 ,前庭水管内口已发育形成。胚胎 10周 ,前庭水管生长延伸至后颅窝的岩锥后壁。到胚胎 3 8周 ,管径各参数均值小于成人前庭水管直径平均值。统计分析显示 ,随胎龄变化前庭水管内口、外口、中点直径呈非线性生长 ,生长曲线无稳定走向趋势 ,仅长度随胎龄增大而增长。结论　整个胚胎期前庭水管处在不断发育过程中 ,出生时横向直径均值无一达成人水平 ,提示 ,前庭水管横径在出生后可能继续发育     

单侧前庭毁损引起的中枢平衡代偿

单侧前庭毁损引起的平衡功能失调导致一系列参与平衡感知和调控的中枢神经核团都会发生相应的代偿性改变.这些参与维持平衡的中枢代偿性调节包括健侧前庭核与患侧前庭核之间的活动协调,视觉动眼系统的代偿性调节、小脑的代偿性改变、网状结构的信号协调,下橄榄核的代偿性调节、丘脑的代偿性丘觉、大脑皮层的平衡调控以及某些适应性行为的改变等...     

Electronystagmographic changes in patients with unilateral vestibular schwannomas in relation to tumor progression and central compensation

Vestibular function was studied in a group of 121 patients with unilateral vestibular schwannomas who were referred to University Hospital Utrecht between 1986 and 1996. Testing included the caloric test, torsion test, saccade test, smooth pursuit test and the registration of spontaneous nystagmus. Each patient’s symptoms were taken from a chart review. The size of the tumor was expressed as the maximum extrameatal diameter in the axial plane parallel to the petrous ridge as seen in magnetic resonance imaging or computed tomography. Large tumors were significantly more often accompanied by a more severe paresis on caloric testing, a smaller gain on torsion testing, spontaneous nystagmus, an abnormal saccade test and an abnormal smooth pursuit test. The presence of spontaneous nystagmus was significantly more frequently combined with an abnormal smooth pursuit and saccade test. There was a significant correlation between the slow component’s velocity of the spontaneous nystagmus and the size and progression of tumor. However, a specific relation between tumor size and central vestibular compensation could not be demonstrated. Received: 5 January 1998 / Accepted: 14 August 1998     

Muscarinic and gamma-aminobutyric acid-ergic receptor changes during vestibular compensation

Summary Involvement of the neurotransmitters acetyl choline and gamma-aminobutyric acid (GABA) in vestibular compensation has been suggested by electrophysiological and pharmacological experiments. In this investigation we used quantitative autoradiography to study the modification of muscarinic and benzodiazepine receptors in each nucleus of the rat's vestibular nucleus complex. Tissues were examined 3, 14, 23 h and 3, 12, 37 and 90 days after unilateral surgical labyrinthectomies. The present results demonstrated a muscarinic receptor supersensitivity in the deafferented side in the suprerior vestibular nucleus 90 days after surgery. This increase was not large enough to support the cholinergic receptor supersensitivity hypothesis for vestibular compensation. The changes in the benzodiazepine receptors observed for a short time following surgery were reversed after a few days. These findings support a transient involvement of GABAergic pathways in vestibular compensation.     

Recovery of vestibular imbalances after vestibular neuritis

OBJECTIVES: To determine chronological characteristics of vestibular recovery after vestibular neuritis (VN) by using various clinical parameters. STUDY DESIGN: Prospective clinical study. METHODS: Twenty of 22 consecutive patients with acute VN underwent serial follow-ups of static (spontaneous nystagmus, subjective visual vertical, and ocular torsion) and dynamic (head-shaking nystagmus [HSN], vibration-induced nystagmus [VIN], head thrust test, and caloric test) vestibular imbalances for 1 year after symptom onset. RESULTS: Static vestibular imbalances improved more rapidly than dynamic imbalances. Among the dynamic imbalances, a trend of higher recovery rate was found in head thrust sign, HSN, and VIN than in caloric asymmetry. HSN tended to be more sensitive in detecting vestibular asymmetry than VIN and head thrust sign. Some patients showed direction reversal of HSN (n = 5, 25.0%) or VIN (n = 5, 25.0%) during follow-up. Direction of VIN changed according to the stimulation sites in four (20.0%) patients. CONCLUSIONS: In view of more rapid resolution of static vestibular imbalance after VN, evaluation of the dynamic vestibular imbalances may provide more useful information for underlying vestibulopathy, especially in the compensated phase. The different temporal profiles ofdynamic vestibular recovery may reflect different chronological characteristics of vestibular compensation according to stimulus frequency. Direction reversal of HSN and VIN during follow-up suggests that lateralization of VNbased on the direction of these nystagmus should be considered in the context of disease phase.     

Compared study of optokinetic and caloric nystagmus in children with unilateral hyporeflexia and other vestibular disorders

The authors compare the nystagmus evoked by the caloric test and by two slow and fast optokinetic 'look' stimulations performed in 78 subjects subdivided into two groups and recorded by ENG: group 1 composed of 22 subjects with 'significative' unilateral hyporeflexia and group 2 composed of 56 subjects with important anomalies at the vestibular caloric test. The results can be summarized as follows: 1. the presence of unilateral vestibular hyporeflexia is not exceptional in the child: 22 over 140 cases (15.7%); 2. the comparison between the caloric test and the OKN test in the 22 subjects with significant unilateral hyporeflexia shows: slow and fast TAP homolateral to the side with labyrinthine deficit prevails in ten subjects (45.4%); TAP is inconsistency with respect to the hyporeflexic side (i.e. homolateral in one test and contralateral in the other) in seven cases (31.8%); TAP is contralateral in five cases (22.7%). Within the same group, STAP varies according to cases. 3. In group II, TAP values at the OKN test overlap considerably with respect to the caloric test (18 cases with a total TAP prevailing on the right side, 32.2%; 19 cases with divergent TAP, 33.9%; 19 cases with total TAP prevailing on the left side, 33.9%). 4. The data shown in group 1 with significant vestibular hyporeflexia can be correlated to the time elapsed between the last electronystagmography and that performed soon after disease onset. Since for ENG performed some days after vertigo onset (even though clinical examination is negative) shows a concordance of OKN TAP and the hyporeflexic side (as the mechanisms of central compensation are still being developed) and then when these mechanisms improve with time, an inconsistency of OKN TAP and hyporeflexic side and finally a contralaterality. We might rely on the comparison between OKN TAP and caloric test as a finding of the time distance from the vertigo onset (when unknown) and a rough prognostic sign. The only case of vestibular neuritis by us followed in time seems to confirm our assumption.