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Mechanism of mitochondrial transcellular transfer in cerebral ischemia-reperfusion injury

AN Rui-Shu^1,2,3, QIN Wen-Xiu^1,2,3, YANG Jian^1,2, XU Jun-Feng^1,2,*

¹Department of Acupuncture, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China；²National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 301617, China；³Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China

Abstract

Ischemic stroke (IS) is an acute cerebrovascular disease in which blood circulation to brain tissue and neurological function are impaired due to obstruction of cerebral blood vessels, and it is one of the most common causes of death worldwide. Therapies such as intravenous thrombolysis and endovascular thrombectomy can open occluded cerebral vessels and restore blood flow through reperfusion, but ischemia/reperfusion (I/R) may trigger pathological processes such as oxidative stress, electrolyte disorders, and inflammatory responses, leading to secondary tissue damage such as cerebral edema and intracranial hemorrhage. Therefore, it is crucial to mitigate cerebral ischemia-reperfusion injury (CIRI). Mitochondria, as organelles, usually exist inside cells. However, under the stimulation of CIRI, mitochondria and their components can affect brain tissue cells by transcellular transfer through tunneling nanotubes (TNTs), gap junctions (GJs), and releasing and capturing of extracellular vesicles (EVs), etc. The mitochondrial transcellular transfer therapy for CIRI can reduce oxidative stress damage, improve neuronal energy metabolism, regulate neuroinflammation, and promote neural repair and regeneration. Mitochondrial transcellular transfer is regarded as a promising therapeutic approach for the treatment of CIRI, and in-depth investigation of the mechanism of mitochondrial transcellular transfer is expected to open up a new clinical pathway for the treatment of CIRI. This paper explores the molecular mechanism of mitochondrial transcellular transfer and its effects in the treatment of CIRI, which is expected to broaden clinical therapeutic approaches and provide a new direction for the treatment of CIRI.

Key words: mitochondrial transcellular transfer; cerebral ischemia-reperfusion injury; ischemic stroke; tunneling nanotube; gap junction

Received: 　　Accepted:

Corresponding author: 许军峰　　E-mail:

DOI: 10.13294/j.aps.2026.0030

Citing This Article：

AN Rui-Shu, QIN Wen-Xiu, YANG Jian, XU Jun-Feng. Mechanism of mitochondrial transcellular transfer in cerebral ischemia-reperfusion injury. Acta Physiol Sin 2026; 78 (2): 295-305 (in Chinese with English abstract).