Edaravone neuroprotection effected by suppressing the gene expression of the Fas signal pathway following transient focal ischemia in rats.
Preclinical and clinical studies have demonstrated that a free radical scavenger edaravone has neuroprotective effects on ischemic stroke but the underlying mechanism is not fully understood. The aim of this research is to explore the effect of edaravone on the apoptotic process involving the Fas/FasL signaling pathway. Transient focal ischemia in rats was induced for 2 hours by middle cerebral artery occlusion (MCAO). After reperfusion rats were treated i.v. with either edaravone or physiological saline. The expression of Fas-associated death domain protein (FADD), death-associated protein (Daxx) and caspase-8 was examined by immunohistochemistry. The mRNA levels for FADD and Daxx by reverse-transcriptase PCR (RT-PCR) and apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Neurological scores and infarction volumes were also evaluated. Edaravone significantly improved the neurological outcome (p<0.05) and reduced the total infarct volumes (p<0.05), compared with saline control. In addition, edaravone-treatment significantly reduced the number of TUNEL-positive cells (p<0.01), reduced expression levels of FADD, Daxx and caspase-8 immunoreactivity (p <0.05 approximately 0.01), and decreased mRNA levels of FADD and Daxx (p<0.05 approximately 0.01) within the peri-infarct area. We conclude that edaravone may protect ischemic neurons from apoptosis via suppressing the gene expression of the Fas/FasL signaling pathway.
Xiao
B
B
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008.
Bi
F-F
FF
Hu
Y-Q
YQ
Tian
F-F
FF
Wu
Z-G
ZG
Mujlli
H M
HM
Ding
L
L
Zhou
X-F
XF
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053938:DNA Fragmentation / Q000187:drug effects; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D000077553:Edaravone; D005786:Gene Expression Regulation / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D018709:Statistics, Nonparametric
D053418:Death Domain Receptor Signaling Adaptor Proteins; D018696:Neuroprotective Agents; D000077553:Edaravone; D000983:Antipyrine