Inhibiting astrocyte calcium dynamics terminates status epilepticus via wireless septal stimulation

  • Sci Rep. 2025 Jul 15;15(1):25579. doi: 10.1038/s41598-025-09611-w.
Chunxiao Tian  #  1 ,  Qiuying Xue  #  2 ,  Tongrui Wu  #  1 ,  Jingyu Zhao  1 ,  Chao Tian  3 ,  Yuxuan Zhu  2 ,  Hualin He  2 ,  Aili Liu  2 ,  Lei Dong  4 ,  Yu Zheng  4 ,  Hui Shen  5
Affiliations
  • 1. School of Biomedical Engineering, Tianjin Medical University, Tianjin, China.
  • 2. School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 3. Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 4. School of Life Sciences, Tiangong University, Tianjin, China.
  • 5. School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. [email protected].
  • # Contributed equally.
PMID: 40664874 DOI: 10.1038/s41598-025-09611-w
Abstract

Status epilepticus (SE) is an acute medical emergency with unclear cellular and circuit mechanisms, and it is imperative to develop anti-SE strategies. Here, we observe distinct astrocytic CA2+ activity patterns during SE: generalized seizures (GS) show synchronized activity between CA3 and contralateral S1, while focal seizures (FS) exhibit desynchronization. Additionally, micrometer-scale wireless electrical stimulation (WES) targeting the medial septum and ventral diagonal band of Broca (MS/vDB) effectively terminates SE and suppresses abnormal astrocytic CA2+ activity, comparable to conventional deep brain stimulation (DBS). The effect is linked to MS/vDB GABAergic neuron activation, which suppresses calcium dynamics within the CA3 astrocyte-pyramidal neuron microcircuit. Meanwhile, WES of the MS/vDB effectively suppresses chronic spontaneous seizures induced by pilocarpine within 10 days. This study shows the divergent patterns of astrocytic activity during SE. It also demonstrates that WES of MS/vDB can effectively suppress SE, establishing an advanced therapeutic strategy.

Keywords
Astrocytes; Ca2+ activity; Focal seizure; Generalized seizure; Wireless electrical stimulation.
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