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An Antioxidant Role by Minocycline Via Enhancing the Activation of LKB1/AMPK Signaling in the Process of Cerebral Ischemia Injury

[ Vol. 18 , Issue. 3 ]

Author(s):

Z. Cai*, C. Wang, Y. Chen and W. He   Pages 142 - 151 ( 10 )

Abstract:


Background: LKB1/AMPK signaling pathway, as a metabolic checkpoint, is involved in the pathogenesis of cerebral ischemia injury. Minocycline, a tetracycline derivative, protects against cerebral ischemia via reducing inflammation, oxidative stress, and apoptosis. The aim of the study was to evaluate the influence of minocycline on oxidative biomarkers and LKB1/AMPK signaling pathway in Wistar rats with focal cerebral ischemia injury and to clarify the neuroprotective mechanism of minocycline against focal cerebral ischemia injury.

Methods: The focal cerebral ischemia injury of Wistar rats was established by inserting a thread into the left middle cerebral artery. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to label infarct volume. The levels of MDA and LPO were measured with a biochemical assay. All other items were determined by Western blotting.

Results: Minocycline decreased cerebral infarct volume, but had no effects on neurological scores. Minocycline improved the biological activity of GPx-1/2, GSS and GR, while limited the GGT1 activity in the hippocampus of cerebral ischemia-reperfusion rats. Minocycline also elevated the biological activity of SOD and counteracted lipid peroxidation. Minocycline enhanced the activity of both LKB1 and the levels of the three AMPK subunits in the hippocampus of cerebral ischemia-reperfusion rats.

Conclusion: Minocycline effectively inhibits oxidative stress via modulating antioxidative enzymes and activating the LKB1/AMPK signaling pathway in the process of acute cerebral infarct.

Keywords:

Cerebral ischemia, energy metabolism, oxidative stress, tetracycline, LKB1/AMPK, minocycline.

Affiliation:

Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400013, Chongqing, Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province



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