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http://dx.doi.org/10.4196/kjpp.2020.24.1.11

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  

Wang, Jieying (Department of Pediatrics, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University)
Bai, Taomin (Department of Pediatrics, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University)
Wang, Nana (Central Laboratory, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University)
Li, Hongyan (Department of Pediatrics, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University)
Guo, Xiangyang (Department of Pediatrics, Shaanxi Provincial People's Hospital, The Affiliated Hospital of Xi'an Medical University, The Third Affiliated Hospital of Xi'an Jiaotong University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.24, no.1, 2020 , pp. 11-18 More about this Journal
Abstract
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-reperfusion-induced 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;
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