Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (11): 2480-2487.doi: 10.4103/1673-5374.390966

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Cav3.2 channel regulates cerebral ischemia/reperfusion injury: a promising target for intervention

Feibiao Dai1, 2, 3, #, Chengyun Hu1, 2, 3, #, Xue Li1, 2, 3, #, Zhetao Zhang3, 4, Hongtao Wang2, 3, Wanjun Zhou2, 3, Jiawu Wang2, 3, Qingtian Geng2, 3, *, Yongfei Dong3, 5, *, Chaoliang Tang2, 3, *   

  1. 1Graduate School, Wannan Medical College, Wuhu, Anhui Province, China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China; 3Core Facility Center for Medical Sciences, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, Anhui Province, China; 4Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China; 5Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China
  • Online:2024-11-15 Published:2024-03-29
  • Contact: Chaoliang Tang, MD, PhD, chaolt@ustc.edu.cn; Yongfei Dong, MD, dyf.w@163.com; Qingtian Geng, MD, gengqingtian@sina.com.
  • Supported by:
    This study was supported by the Natural Science Foundation of Anhui Province of China, No. 2208085Y32; Scientific Research Plan Project of Anhui Province of China, No. 2022AH020076; and the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province, No. CXPJJH12000005-07-115 (all to CT).

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Abstract: Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury. Various calcium channels are involved in cerebral ischemia/reperfusion injury. Cav3.2 channel is a main subtype of T-type calcium channels. T-type calcium channel blockers, such as pimozide and mibefradil, have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury. However, the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear. Here, in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons. The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons. We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury. Cav3.2 knockout markedly reduced infarct volume and brain water content, and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury. Additionally, Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress, inflammatory response, and neuronal apoptosis. In the hippocampus of Cav3.2-knockout mice, calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury. These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling. Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

Key words: calcineurin, Cav3.2 channel, cerebral ischemia/reperfusion, hippocampus, hypoxia/reoxygenation, inflammatory response, nuclear factor of activated T cells 3, oxidative stress, primary hippocampal neurons, stroke