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

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Jieying Wang Taomin Bai Nana Wang Hongyan Li Xiangyang Guo
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제24권 제1호, 11~18쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2020.01.31

영문 초록

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.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

키워드

Connexin 43 Imatinib mesylate Ischemia Neuroprotection Reperfusion STAT3 transcription factor