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| 1 | An Animal Model of Sudden Onset Sensorineural Hearing Loss with Vestibular Function Disturbances Induced By Mitochondrial Toxin显示文摘Objective To establish an animal model of sudden onset sensorineural hearing loss (SSNHL) to study its mechanisms. Materials and methods The inner ear was exposed to 3-nitropropionic acid at 0.5 mol/L (3-NP (H)) and 0.3 mol/L (3-NP (L)) through the round window membrane for 30 minutes in 50 male guinea pigs. Thresholds of auditory brainstem responses(ABR) were established before the treatment and retested at 4 hours, 1 day, 3 days and 6 days following 3-NP exposure. Control animals were treated with phosphate buffered saline (PBS) and their ABRs were retested at 4 hours and 1 day after the treatment. Animals were monitored for nystagmus and postural signs of vestibular dysfunction, using a digital video camera, following the treatment procedure. Specimens were taken at 12 hours, 1 day, 3 days and 7 days following 3-NP(H) exposure and embedded in JB4 for light microscopy observation. Results ABRs were lost in all animals tested at 4 hours following 3-NP (H) exposure. The rate of complete ABR loss decreased as post-treatment test time increased. ABRs were lost in 80% (4/5) of the animals at 1 day after exposure to 3-NP (L). Spontaneous horizontal nystagmus with a fast phase away from the treated ear developed in all 3-NP (H)-treated animals and in 20 % ( 1/5) of the animals exposed to 3-NP (L), except for the one treated bilaterally. Various degree of postural disturbances consistent with unilateral vestibular dysfunction, such as spontaneous barrel rolling towards the exposure side while walking, were seen in all animals exposed to 3-NP(H) and 40% (2/5) of animals exposed to 3-NP(L), except for the one animal treated bilaterally, which showed no signs of imbalance. Both nystagmus and postural disturbances resolved in 2 days following 3-NP exposure. Histological study showed temporary edema tin the organ or Corti, Claudius cells and the inner sulcus cells 3 days after 3-NP (H) treatment. Enlargement of intercellular space in the spiral prominence was first noticed at 12 hours post-3-NP (H) exposure, progressed at day 3 and recovered at day 7. Vacuoles in the cellular plasm and nucleus was seen as early as at 12 hours post-3-NP exposure in the spiral ganglion cells, and signs of degeneration were visible at day 7. Conclusion Inner ear exposure to 3-NP through the round window membrane appears to reproduce clinic manifestations and may serve as a legitimate animal model of | PYYKK Ilmari | 2006 | Journal of Otology2006，1，2： | 1 |
| 2 | 用MRI体内观测钥孔嘁血蓝素中耳免疫诱导的内淋巴积水的初步探讨显示文摘目的用磁共振成像方法研究中耳免疫反应诱导的动物内淋巴积水。方法将9只豚鼠分为2组,中耳免疫组(4只)和磷酸盐缓冲液(Phosphate buffered saline,PBS)对照组(5只)。先用KLH加福氏完全佐剂行四肢趾蹼免疫,2周后将KLH投放至中耳进行局部免疫。另外5只豚鼠中耳放置PBS作为对照组。用gadolinium增强的磁共振成像观察内耳淋巴液的动态变化,用耳蜗电图评估听功能改变。结果在KLH中耳免疫的动物中,2只发生内淋巴积水,3只血迷路屏障通透性增加,2只听力损失大于10dB。结论磁共振成像可以显示KLH中耳免疫反应的耳蜗改变,内淋巴积水和血迷路屏障通透性的增加提示存在着一个“漏的迷路”,将有可能为内耳疾病的诊断提供更加精确的依据。 | 邹静 Ilmari PYYKK Brje BJELKE | 2005 | 中华耳科学杂志2005，3，3： | 4 |
| 3 | 耳蜗振动创伤后血迷路屏障变化的磁共振成像表现显示文摘目的在动物模型中探讨电钻振动诱导听力减退的机制和可能的血迷路屏障变化。方法用电磁振荡器在5只豚鼠听泡上产生可重复的振动,其振动频率为250 Hz,用复合动作电位评估其听功能,振动后3小时至4 天用4.7特斯拉磁共振成像分析其血迷路屏障变化。静脉注射T1增强剂Gadolinium-diethylenetriaminepentaacetate- bismethylamide(Gd-DTPA-BMA)作为血迷路屏障的示踪剂。结果振动诱导平均听力损失40 dB HL,在振动后立即测试的耳蜗中,其中阶摄取Gd-DTPA-BMA,提示血迷路屏障通透性增加。在振动后2天至4天的动物中,其中阶内无Gd-DTPA-BMA摄取。结论 250 Hz振动使血路屏障通透性增加是使导致听力减退的原因之一。其通透性的变化为一个可逆的过程。 | 邹静 Ilmari Pyykk Pivi Sutinen Esko Toppila | 2006 | 中华耳科学杂志2006，4，1： | 1 |
| 4 | 用4.7特斯拉磁共振成像活体内观测豚鼠实验性内淋巴积水显示文摘目的探讨用4.7特斯拉试验用磁共振成像系统能否在豚鼠中检测内淋巴积水。方法20只白色或者杂色豚鼠用于该研究。5只正常豚鼠作为对照组,15只豚鼠用于制作内淋巴积水模型。9只内淋巴囊破坏组中的5只和6只内淋巴囊完整组(与乙状窦游离)动物采用gadolinium(Gd)-DTPA-BMA增强MRI检测内淋巴积水。结果由于Gd-DTPA-BMA主要进入鼓阶和前庭阶,耳蜗的三个阶可在所有动物中由MRI清晰显示。在内淋巴囊完整组,内淋巴囊手术后6天MRI即可检测到内淋巴积水,并且由组织学证实。在内淋巴囊破坏组中的1只动物,因内耳屏障的严重破坏而使Gd-DTPA-BMA快速漏入中阶,MRI可检测到该变化,其听力损失为60dB。结论用Gd-DTPA-BMA增强的高分辨MRI可检测出内淋巴积水,有可能对积水程度进行定量测试。在Gd-DTPA-BMA的帮助下,内耳屏障损伤或可能的膜破裂可以被检出。 | 邹静 Ilmari Pyykk Poul Bretlau Tomas Klason Brje Bjelke | 2005 | 中华耳科学杂志2005，3，3： | 1 |
| 5 | Nanoparticle based inner ear therapy显示文摘Synthetic nanoparticles can be used to carry drugs, genes, small interfering RNA(si RNA) and growth factors into the inner ear, to repair, restore and induce cellular regeneration. Nanoparticles(NPs) have been developed which are targetable to selected tissue, traceable in vivo, and equipped with controlled drug/gene release. The NPs are coated with a ‘stealth' layer, and decorated with targeting ligands, markers, transfection agents and endosomal escape peptides. As payloads, genes such as the BDNF-gene, Math1-gene and Prestin-gene have been constructed and delivered in vitro. Short-hairpin RNA has been used in vitro to silence the negative regulator of Math1, the inhibitors of differentiation and DNA binding. In order to facilitate the passage of cargo from the middle ear to the inner ear, the oval window transports gadolinium chelate more efficiently than the round window and is the key element in introducing therapeutic agents into the vestibule and cochlea. Depending upon the type of NPs, different migration and cellular internalization pathways are employed, and optimal carriers should be designed depending on the cargo. The use of NPs as drug/gene/si RNA carriers is fascinating and can also be used as an intraoperative adjunct to cochlear implantation to attract the peripheral processes of the cochlear nerve. | Ilmari Pyykk Jing Zou Ya Zhang Weikai Zhang Hao Feng Paavo Kinnunen | 2013 | World Journal of Otorhinolaryngology2013，3，4： | 0 |
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