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Original Article

Korean J Physiol Pharmacol 2020; 24(1): 11-18

Published online January 1, 2020 https://doi.org/10.4196/kjpp.2020.24.1.11

Copyright © The Korean Journal of Physiology & Pharmacology.

Neuroprotective potential of imatinib in global ischemia-reperfusion-induced cerebral injury: possible role of Janus-activated kinase 2/signal transducer and activator of transcription 3 and connexin 43

Jieying Wang1, Taomin Bai1, Nana Wang2, Hongyan Li1, and Xiangyang Guo1,3,*

1Department of Pediatrics and 2Central Laboratory, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710068, 3Department of Neurology, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China

Correspondence to:*Xiangyang Guo
E-mail: sxxaped@sina.com

Received: May 17, 2019; Revised: June 18, 2019; Accepted: June 20, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusioninduced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.

Keywords: Connexin 43, Imatinib mesylate, Ischemia, Neuroprotection, Reperfusion, STAT3 transcription factor