Neuroprotective effect of SP600125, an inhibitor of JNK on brain ischemia/reperfusion in rats

Objective To investigate the effect of SP600125 on cell apoptosis in hippocampal CA1 after cerebral ischemia/reperfusion (I/R) in rats and its possible mechanism.Methods 54 SD rats weighing 230 g-250 g were randomly divided into sham operation group (SH),I/R group and JNK inhibitor SP600125 group (SP).The rats received intracerebroventricularly DMSO(SH group),DMSO(I/R group) and SP600125(SP group,the use of DMSO solvent) 30 min before ischemia.Each group was divided into 3 subgroups according to reperfusion time 30 min,24 h and 72 h (6 animals for each subgroup).Global cerebral ischemia was induced by four-vessel occlusion in rats.Behavioral test was performed at 24 h and 72 h after cerebral ischemia/reperfusion.Bax and Bcl-2 positive pyramidal cells as well as apoptotic positive pyramidal cells in the CA1 were quantified in immunohistochemical stained or terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL) stained sections.Results Compared with SH group,cerebral I/R induced a decrease in standing times(4.8±2.0 vs 9.1±3.4,P＜0.05) and the beam-walking test scores(2.3±l.2 vs 3.5±0.9,P＜0.05).Immunohistochemistry results showed that after ischemia/reperfusion Hippocampal CA1 area Bcl-2 and Bax positive expression increased the number of pyramidal cells,24 h of reperfusion the number of pyramidal cells shows that the expression of positive to the peak(40.5±5.1)(P＜0.01),After I/R 24 h to 72 h,Positive expression to reduce the number of pyramidal cells (P＜0.05),With the IR group,SP group Bcl-2-positive pyramidal cells increased the number of (89.7±8.4)(P＜0.05),Baxpositive increase in the number of pyramidal cells less (40.5±2.3)(P＜0.05).Conclusions SP600125 protects hippocampal CA1 neurons from death during global brain ischemia/reperfusion injury through inhibition of JNK signal transduction pathway. Key words: Brain ischemia;  Reperfusion injury;  Apoptosis;  JNK;  Bcl-2;  Bax