Department of Physiology and Neuroscience Care Unit, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China.
Key Laboratory of the Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, 310009, China.
Cerebellum. 2024 Apr;23(2):329-339. doi: 10.1007/s12311-023-01531-7. Epub 2023 Feb 15.
The most common clinical manifestation of sepsis-related encephalopathy (SAE) is the deterioration of cognitive function. Besides, increasing evidence shows that SAE patients exhibit coordination and sensorimotor dysfunctions, suggesting that SAE affects motor function with unclear mechanism. In the present work, we explored the effects of SAE on cerebellar Purkinje cells (PCs) using cecal ligation and perforation (CLP), a standard model for inducing sepsis symptoms similar to those in human patients. Our results show that the sepsis can activate microglia in the cerebellum and promote the secretion of inflammatory factor TNF-α, which increases intrinsic excitability and synaptic transmission of PCs, inhibits the synaptic plasticity of PCs, and impairs motor learning of mice. These findings address how SAE changes PC functions, and thereby are of great significance to reveal pathophysiological feathers of human patients suffering from SAE.
脓毒症相关性脑病（SAE）最常见的临床表现是认知功能恶化。此外，越来越多的证据表明，SAE 患者表现出协调和感觉运动功能障碍，这表明 SAE 以不明机制影响运动功能。在本工作中，我们使用盲肠结扎穿孔（CLP）研究了 SAE 对小脑浦肯野细胞（PCs）的影响，CLP 是一种诱导类似于人类患者的脓毒症症状的标准模型。我们的结果表明，脓毒症可以激活小脑中的小胶质细胞并促进炎症因子 TNF-α的分泌，这增加了 PCs 的内在兴奋性和突触传递，抑制了 PCs 的突触可塑性，并损害了小鼠的运动学习。这些发现说明了 SAE 如何改变 PCs 的功能，因此对于揭示患有 SAE 的人类患者的病理生理特征具有重要意义。
