Ionic-network dysregulation in the brain: Mechanisms, diseases, and therapeutic strategies

Siyi Han; Enduo Feng; Lize Xiong

doi:10.59717/j.xinn-tine.2026.100015

The Innovation Neurology > 2026 Vol. 1 > No. 1 > 100015

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Ionic-network dysregulation in the brain: Mechanisms, diseases, and therapeutic strategies

1.
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China

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Corresponding authors: edfeng@tongji.edu.cn (E.F.); mzkxlz@126.com; lizexiong@tongji.edu.cn (L.X.)
Received Date: July 14, 2026

Accepted Date: September 07, 2026

Published Online: September 09, 2026

The Innovation Neurology 1(1), https://doi.org/10.59717/j.xinn-tine.2026.100015 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Ion imbalance is a key molecular event in many neurological disorders.
  
  Altered Ca²⁺, Fe^2+/3+, Cu^+/2+, Zn²⁺, Na⁺, K⁺, Cl^-, and Mg²⁺ disrupt brain function.
  
  Shared ionic mechanisms link neurodegeneration, stroke, epilepsy and perioperative cognitive disorders.
  
  Artificial intelligence may help decode multidimensional ion networks in brain diseases.
  
  Existing therapies target parts of ionic network, but ionomics-guided strategies remain emerging frontiers.

ABSTRACT

ABSTRACT

Ionic homeostasis is a fundamental organizing principle of brain function, supporting electrical signaling, metabolic coupling, cellular communication, and neurovascular stability. Ionic-network dysregulation has emerged as an important mechanism of neurological diseases. Herein, we review the physiological architecture of brain ionic homeostasis and its dynamic organization across spatial and temporal scales. We then discuss the involvement of ionic network dysregulation in pathological cascades, including excitability imbalance, mitochondrial injury, redox stress, metal-dependent cell death, protein misfolding, neuroinflammation and barrier dysfunction and their involvement in representative neurological diseases. Furthermore, we discuss the potential role of multimodal chemical analysis and artificial intelligence in decoding ionic characteristics in neurological diseases. Finally, we review established and experimental therapies targeting ion channels, redox pathways, metal dyshomeostasis and chloride transport. This review provides an integrated framework for understanding ionic-network dysregulation as both a driver of neurological disease and a promising target for precision diagnosis, risk stratification, and mechanism-guided intervention.

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Han S., Feng E. and Xiong L. (2026). Ionic-network dysregulation in the brain: Mechanisms, diseases, and therapeutic strategies. The Innovation Neurology 1:100015. https://doi.org/10.59717/j.xinn-tine.2026.100015

Han S., Feng E. and Xiong L. (2026). Ionic-network dysregulation in the brain: Mechanisms, diseases, and therapeutic strategies. The Innovation Neurology 1:100015. https://doi.org/10.59717/j.xinn-tine.2026.100015

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