Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Regulating Mitophagy via mTOR-ULK1/FUNDC1 Axis in Rats

• DOI: 10.1016/j.jstrokecerebrovasdis.2021.106202
• Publication Date: 2021-11-11T23:43:53Z
• Authors: Weiqian Tian; Minmin Zhu; Yudi Zhou; Chenlu Mao; Rong Zou; Yaomei Cui; Sha Li; Juan Zhu; Cheng Hu
• Keywords: Male; Sirolimus; 0301 basic medicine; TOR Serine-Threonine Kinases; Mitophagy; Membrane Proteins; Infarction, Middle Cerebral Artery; Mechanistic Target of Rapamycin Complex 1; Brain Ischemia; Rats; Mitochondrial Proteins; Rats, Sprague-Dawley; 03 medical and health sciences; Electroacupuncture; Reperfusion Injury; Animals; Autophagy-Related Protein-1 Homolog

Electroacupuncture (EA) pretreatment has been shown to alleviate cerebral ischemia-reperfusion (I/R) injury; however, the underlying mechanism remains unclear. To investigate the involvement of mTOR signaling in the protective role of EA in I/R-induced brain damage and mitochondrial injury.Sprague-Dawley male rats were pretreated with vehicle, EA (at Baihui and Shuigou acupoints), or rapamycin + EA for 30 min daily for 5 consecutive days, followed by the middle cerebral artery occlusion to induce I/R injury. The neurological functions of the rats were assessed using the Longa neurological deficit scores. The rats were sacrificed immediately after neurological function assessment. The brains were obtained for the measurements of cerebral infarct area. The mitochondrial structural alterations were observed under transmission electron microscopy. The mitochondrial membrane potential changes were detected by JC-1 staining. The alterations in autophagy-related protein expression were examined using Western blot analysis.Compared with untreated I/R rats, EA-pretreated rats exhibited significantly decreased neurological deficit scores and cerebral infarct volumes. EA pretreatment also reversed I/R-induced mitochondrial structural abnormalities and loss of mitochondrial membrane potential. Furthermore, EA pretreatment downregulated the protein expression of LC3-II, p-ULK1, and FUNDC1 while upregulating the protein expression of p-mTORC1 and LC3-I. Rapamycin effectively blocked the above-mentioned effects of EA.EA pretreatment at Baihui and Shuigou alleviates cerebral I/R injury and mitochondrial impairment in rats through activating the mTORC1 signaling. The suppression of autophagy-related p-ULK1/FUNDC1 pathway is involved in the neuroprotective effects of EA.