Study Of Apoptotic Genes Expression And Effect Of Edaravone On Them Following Focal Cerebral Ischemia/Reperfusion In Rats

Background and objective: Many genes modulate the neuronal apoptosis following ischemia brain damage. There are mainly two apoptotic signal transduction pathways modulated by death receptor Fas, one is Fas-FADD-Caspase-8 pathway, the other is Fas-Daxx-ASK1 pathway. FADD (Fas-associated death domain protein) and caspase-8, especially, play an important role in many apoptotic pathways modulated by death receptors. Daxx (death-associated protein), which play an important role on gene transcription and apoptosis. In contrast, FasR possesses a unique carboxy-terminal domain shown to be important for interaction with a protein-tyrosine phosphatase (Fas associated phosphatase-1, FAP-1) whose expression appears to be correlated with the inhibition of FasR mediated cell death. Whereas the expression and effect of FADD, FAP-1 and Daxx following ischemia brain damage were seldom reported. Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by clinical use. Although it can decrease the neuronal apoptosis in ischemic brain models, the mechanism is kept unclear. In order to explore the molecular pathological mechanism of cerebral ischemia/reperfusion and the role of edaravone in ischemic neuronal apoptosis, the present study is performed to define the expression of apoptosis associated genes FADD, FAP-1, Daxx and caspase-8 protein and/or mRNA and their association with brain damage after cerebral ischemia/reperfusion in rats.Methods: 186 Male Sprague-Dawley rats weighing 250±20g were randomly divided into four groups: normal group (n=6), sham-operated control group (n=60), cerebral ischemia model group (n=60) and edaravone-treated group (n=60). Temporary middle cerebral artery occlusion (MCAO) model was applied. Immediately and 12 h after reperfusion, rats received intraperitoneal injections of 3.0mg/kg of edaravone for the edaravone-treated group and same volume physiological saline for the cerebral ischemia model group. The expression of FADD, FAP-1, Daxx and caspase-8 protein and/or mRNA were measured with meathods of immunohistochemistry, Western blot...