Profiling the rat cortical single-cell transcriptome reveals the potential mechanism of specific mode electroacupuncture stimulation opening the blood-brain barrier

The existence of the blood-brain barrier (BBB) dramatically limits the drug treatment of central nervous system diseases such as stroke, neurodegenerative diseases, and brain tumors. Due to the complexity of the structure and function of the blood-brain barrier, it has been challenging to develop central nervous system drug delivery strategies and reveal critical biological mechanisms. Our previous studies have confirmed that specific mode electroacupuncture stimulation (EA) can effectively open the BBB in rats. Here, we utilized single-cell RNA sequencing (scRNA-seq) to map the cell population of rat cerebral cortex comprehensively. We identified 23 cell subsets and 8 types of cells in the brain obtained by cell annotation, and explored the potential mechanism of EA to open the blood-brain barrier by bioinformatics analysis of specific cell subsets and cell types, as well as cell communications. In summary, scRNA-seq uncovers the transcriptional changes of the cerebral cortex under EA at the single cell level; our results provide rich insights into the molecular and cellular architecture changes of the brain after EA intervention and provide a new reference for BBB material transport and its drug delivery research in health and disease, providing new potential strategies into the mechanism of BBB opening and provide essential information for designing rational treatment regimens and optimizing drug delivery.血脑屏障（blood-brain barrier, BBB）的存在极大限制了脑卒中、神经退行性疾病、脑肿瘤等中枢神经系统疾病的药物治疗。由于血脑屏障的结构与功能兼具复杂性，开发中枢神经系统药物递送策略并揭示其关键生物学机制一直是颇具挑战性的课题。本团队前期研究已证实，特定模式的电针刺激（electroacupuncture stimulation, EA）可有效打开大鼠体内的血脑屏障。本研究利用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对大鼠大脑皮层的细胞群体进行了全景式绘制。通过细胞注释，我们成功鉴定出大鼠脑组织内的23个细胞亚群与8种细胞类型，并通过针对特定细胞亚群、细胞类型以及细胞通讯的生物信息学分析，探索了电针开放血脑屏障的潜在作用机制。综上，单细胞RNA测序技术在单细胞层面揭示了电针干预后大脑皮层的转录水平变化；本研究结果为解析电针干预后大脑的分子与细胞结构改变提供了丰富视角，同时为血脑屏障物质转运及其在健康与疾病状态下的药物递送研究提供了全新参考，为阐明血脑屏障开放的潜在机制提供了新的可行策略，并为合理设计治疗方案、优化药物递送体系提供了关键依据。