Peusner Kenna D, Bell Nina M, Hirsch June C, Beraneck Mathieu, Popratiloff Anastas
Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Université de Paris, Integrative Neuroscience and Cognition Center, CNRS UMR 8002, Paris, France.
Front Neurol. 2021 Sep 10;12:708395. doi: 10.3389/fneur.2021.708395. eCollection 2021.
In congenital vestibular disorders (CVDs), children develop an abnormal inner ear before birth and face postnatal challenges to maintain posture, balance, walking, eye-hand coordination, eye tracking, or reading. Only limited information on inner ear pathology is acquired from clinical imaging of the temporal bone or studying histological slides of the temporal bone. A more comprehensive and precise assessment and determination of the underlying mechanisms necessitate analyses of the disorders at the level, which can be achieved using animal models. Two main criteria for a suitable animal model are first, a pathology that mirrors the human disorder, and second, a reproducible experimental outcome leading to statistical power. With over 40 genes that affect inner ear development, the phenotypic abnormalities resulting from congenital vestibular disorders (CVDs) are highly variable. Nonetheless, there is a large subset of CVDs that form a common phenotype of a sac-like inner ear with the semicircular canals missing or dysplastic, and discrete abnormalities in the vestibular sensory organs. We have focused the review on this subset, but to advance research on CVDs we have added other CVDs not forming a sac-like inner ear. We have included examples of animal models used to study these CVDs. Presently, little is known about the central pathology resulting from CVDs at the cellular level in the central vestibular neural network, except for preliminary studies on a chick model that show significant loss of second-order, vestibular reflex projection neurons.
在先天性前庭疾病（CVDs）中，儿童在出生前内耳就发育异常，出生后面临维持姿势、平衡、行走、眼手协调、眼球追踪或阅读等方面的挑战。从颞骨的临床影像学检查或研究颞骨组织学切片中，只能获取有限的内耳病理学信息。要更全面、精确地评估和确定潜在机制，需要在细胞水平对这些疾病进行分析，而这可以通过动物模型来实现。合适的动物模型有两个主要标准：第一，其病理学特征能反映人类疾病；第二，实验结果具有可重复性，能产生统计学效力。影响内耳发育的基因有40多种，先天性前庭疾病（CVDs）导致的表型异常高度可变。尽管如此，有很大一部分CVDs会形成一种共同的表型，即内耳呈囊状，半规管缺失或发育不良，前庭感觉器官存在离散性异常。我们将综述重点放在了这一亚组疾病上，但为了推进对CVDs的研究，我们也纳入了其他未形成囊状内耳的CVDs。我们还列举了用于研究这些CVDs的动物模型实例。目前，除了对雏鸡模型的初步研究表明二阶前庭反射投射神经元有显著损失外，对于CVDs在中枢前庭神经网络细胞水平上导致的中枢病理学情况知之甚少。
