Modulation of neuronal death by the transcription factor E2F1 in experimental stroke

Since cultured neurons which are deficient in the transcription factor E2F1 display a resistance to a wide variety of insults, studies were undertaken to see if this resistance extended to a cerebral ischemic insult. Following 2 h of left middle cerebral artery occlusion and 1d of reperfusion a 33% smaller infarct (p<0.05) was observed by 2,3,5 triphenyltetrazolium staining in the brains of E2F1-null animals compared to E2F1 +/+ and +/- littermate mice. No differences in physiological parameters or cerebrovasculature were observed in the three groups of animals. A milder ischemic insult produced by 20 min of MCA occlusion and 7 d of reperfusion produced a greater difference in the E2F1-null animals with a 71% smaller infarct (p<0.001) compared to littermate controls. A decrease in ischemic injury in E2F1-null mice was also observed by immunohistochemical monitoring of the neuronal-specific MAP2 cytoskeletal protein and TUNEL staining. Finally a battery of six tests of motor function showed both E2F1 +/+ and littermates were similarly impaired at 1 d of reperfusion, but by 7 d the E2F1 mice improved significantly better compared to the wild type mice (p<0.01) and ended up only slightly impaired by that time. It is concluded that the transcription factor E2F1 does modulate neuronal viability in brain after cerebral ischemia.