Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Stroke Vasc Neurol. 2023 Dec 29;8(6):444-452. doi: 10.1136/svn-2022-002235.
Small subcortical infarcts account for up to 25% of ischaemic strokes. Thalamus is one of the subcortical structures that commonly manifest with lacunar infarcts on MRI of the brain. Studies have shown that thalamus infarction is associated with cognitive decline. However, due to the lack of proper animal models, little is known about the mechanism. We aimed to establish a focal thalamus infarction model, characterise the infarct lesion and assess functional effects.
Male C57BL/6J mice were anaesthetised, and Rose Bengal dye was injected through the tail vein. The right thalamus was illuminated with green laser light by stereotactic implantation of optic fibre. Characteristics of the infarct and lesion evolution were evaluated by histological analysis and 7T MRI at various times. The cognitive and neurological functions were assessed by behavioural tests. Retrograde tracing was performed to analyse neural connections.
An ischaemic lesion with small vessel occlusion was observed in the thalamus. It became a small circumscribed infarct with reactive astrocytes accumulated in the infarct periphery on day 21. The mice with thalamic infarction demonstrated impaired learning and memory without significant neurological deficits. Retrogradely labelled neurons in the retrosplenial granular cortex were reduced.
This study established a mouse model of thalamic lacunar infarction that exhibits cognitive impairment. Neural connection dysfunctions may play a potential role in post-stroke cognitive impairment. This model helps to clarify the pathophysiology of post-stroke cognitive impairment and to develop potential therapies.
小的皮质下梗死占缺血性中风的 25%。丘脑是常见的 MRI 显示腔隙性梗死的皮质下结构之一。研究表明，丘脑梗死与认知能力下降有关。然而，由于缺乏适当的动物模型，对其发病机制知之甚少。我们旨在建立一个局灶性丘脑梗死模型，描述梗死病变，并评估功能影响。
雄性 C57BL/6J 小鼠麻醉后，通过尾静脉注射 Rose Bengal 染料。通过立体定位植入光纤，用绿光激光照射右侧丘脑。通过组织学分析和不同时间的 7T MRI 评估梗死和病变演变的特征。通过行为测试评估认知和神经功能。进行逆行示踪以分析神经连接。
在丘脑观察到小血管闭塞引起的缺血性病变。在第 21 天，它变成了一个小的局限性梗死，梗死周围有反应性星形胶质细胞聚集。丘脑梗死的小鼠表现出学习和记忆受损，而无明显的神经功能缺损。在扣带回后颗粒皮质中的逆行标记神经元减少。
本研究建立了一种表现出认知障碍的小鼠丘脑腔隙性梗死模型。神经连接功能障碍可能在中风后认知障碍中起潜在作用。该模型有助于阐明中风后认知障碍的病理生理学，并开发潜在的治疗方法。
