Carraro Mattia, Almishaal Ali, Hillas Elaine, Firpo Matthew, Park Albert, Harrison Robert V
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Auditory Science Laboratory, Neuroscience and Mental Health Program, The Hospital for Sick Children, Toronto, ON, Canada.
J Assoc Res Otolaryngol. 2017 Apr;18(2):263-273. doi: 10.1007/s10162-016-0606-4. Epub 2016 Dec 19.
Cytomegalovirus (CMV) infection is one of the most common causes of congenital hearing loss in children. We have used a murine model of CMV infection to reveal functional and structural cochlear pathogenesis. The cerebral cortex of Balb/c mice (Mus musculus) was inoculated with 2000 pfu (plaque forming units) of murine CMV on postnatal day 3. At 6 weeks of age, cochlear function was monitored using auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measures. Histological assessment of cochlear vasculature using a corrosion cast technique was made at 8 weeks. Vascular casts of mCMV-damaged cochleas, and those of untreated control animals, were examined using scanning electron microscopy. We find very large variations in the degree of vascular damage in animals given identical viral injections (2000 pfu). The primary lesion caused by CMV infection is to the stria vascularis and to the adjacent spiral limbus capillary network. Capillary beds of the spiral ligament are generally less affected. The initial vascular damage is found in the mid-apical turn and appears to progress to more basal cochlear regions. After viral migration to the inner ear, the stria vascularis is the primary affected structure. We suggest that initial auditory threshold losses may relate to the poor development or maintenance of the endocochlear potential caused by strial dysfunction. Our increased understanding of the pathogenesis of CMV-related hearing loss is important for defining methods for early detection and treatment.
巨细胞病毒（CMV）感染是儿童先天性听力损失最常见的原因之一。我们使用了CMV感染的小鼠模型来揭示耳蜗的功能和结构发病机制。在出生后第3天，给Balb/c小鼠（小家鼠）的大脑皮层接种2000个空斑形成单位（pfu）的鼠巨细胞病毒。在6周龄时，使用听性脑干反应（ABR）和畸变产物耳声发射（DPOAE）测量来监测耳蜗功能。在8周时，使用铸型技术对耳蜗血管系统进行组织学评估。使用扫描电子显微镜检查感染mCMV的耳蜗和未处理的对照动物的血管铸型。我们发现，给予相同病毒注射量（2000 pfu）的动物，其血管损伤程度存在很大差异。CMV感染引起的主要病变位于血管纹和相邻的螺旋缘毛细血管网。螺旋韧带的毛细血管床通常受影响较小。最初的血管损伤出现在蜗顶中部，并似乎向耳蜗更基部的区域发展。病毒迁移到内耳后，血管纹是主要受影响的结构。我们认为，最初的听觉阈值损失可能与血管纹功能障碍导致的内淋巴电位发育不良或维持不佳有关。我们对CMV相关性听力损失发病机制的进一步了解对于确定早期检测和治疗方法很重要。
