单细胞转录组揭示海马深部脑刺激促进缺血性卒中神经修复的机制

Abstract

Background In patients with ischemic stroke, the hippocampus is one of the most severely damaged regions of the brain; however, the optimal parameters for hippocampal deep brain stimulation in these patients remain unknown. The underlying mechanism of hippocampal deep brain stimulation in the treatment of ischemic stroke is not fully understood. Objective To investigate the effect and underlying mechanisms by which hippocampal deep brain stimulation enhances the repair of brain damage from ischemic stroke. Methods We utilized multi-channel electrode arrays to record local field potentials and to monitor motor symptoms in mice with ischemic stroke during deep brain stimulation in hippocampus. Using 10x single-cell transcriptome sequencing and RNA-seq in stroke mice with and without electrostimulation treatment, we explored the underlying mechanisms. Results After being treated with hippocampal deep brain stimulation, the stroke mice showed significant improvements in motor ability, neuronal function, and behaviors related to anxiety/depression. Bioinformatics analysis and subsequent investigations revealed a significant increase in the quantity of excitatory neurons and astrocytes in the hippocampus following deep brain stimulation while the number of oligodendrocytes, microglia and inhibitory neurons was markedly diminished. The microglia subset 5 showed a significant increase following deep brain stimulation treatment, while subsets 3 and 4 experienced a significant reduction. Within subset 5, markers such as Cd93 , Ccr2 , Emilin2 , Pirb , Lgals3 , Thbs1 , Gpnmb , and Ccr1 were associated with immune inflammation and angiogenesis. Conclusion Collectively, our findings imply that hippocampal deep brain stimulation is highly effective for treating ischemic stroke and offer deeper insights into the potential mechanisms by which hippocampal deep brain stimulation improves stroke symptoms. These findings support hippocampal deep brain stimulation as a promisin