Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.

在成年猫单侧前庭神经切断术后的去传入前庭神经核（vestibular nuclei）中，可观测到功能性神经发生与反应性星形胶质发生。新生细胞可存活长达1个月，并积极参与姿势运动功能的成功恢复。本研究旨在探究前庭去传入的类型是否会影响前庭神经核的神经发生潜能，以及行为恢复的时间进程。本研究采用三种模拟不同前庭病理的动物模型：通过单侧前庭神经切断术（unilateral vestibular neurectomy, UVN）或单侧迷路切除术（unilateral labyrinthectomy, UL，即对外周前庭感受器进行机械性损毁）实现单侧永久性前庭输入阻断，或使用河豚毒素（tetrodotoxin, TTX）实现单侧可逆性前庭神经输入阻滞。以5-溴脱氧尿苷（bromodeoxyuridine, BrdU）作为新生细胞标记物，标记前庭神经核内的神经发生与星形胶质发生；同时分别采用胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）与谷氨酸脱羧酶67（glutamate decarboxylase 67, GAD67）鉴定星形胶质细胞与γ-氨基丁酸能神经元。通过自发性眼球震颤与姿势运动测试（静态与动态平衡能力评估）量化行为恢复过程。结果显示，前庭功能丧失的类型决定了前庭神经核内发生的细胞可塑性事件，并影响行为恢复的时间进程。值得注意的是，仅在急性完全性前庭丧失（UVN模型）中，去传入的前庭神经核才会表现出神经发生潜能；而当前庭去传入程度较轻时（UL、TTX模型），则涉及非结构性可塑性过程。本研究首次通过实验证实，脑干中的前庭复合体在特定损伤条件下可产生神经发生。这些新数据有助于从脑修复的视角理解成年哺乳动物中功能性神经发生的表达促进因素，且在前庭病理领域具有临床相关性。