Bifemelane hydrochloride enhances 'ischemic tolerance' phenomenon in gerbil hippocampal CA1 neurons

Neurons are so vulnerable to ischemic insults that transient forebrain ischemia for 5 min killed most CA1 neurons in the gerbil hippocampus (surviving neurons: 4%). In contrast, 2 days after a nonlethal challenge of 2-min ischemia, 51% of CA1 neurons became resistant to subsequent, otherwise lethal ischemia for 5 min. Bifemelane hydrochloride (20 mg/kg, i.p.), which helps ischemic brain recover from oxidative stress and inhibition of protein synthesis, significantly enhanced the 'ischemic tolerance' phenomenon if injected 1 day after 2-min ischemia: 94% of neurons survived after 5-min ischemia. This finding carries implications for possible preventive treatment following warning signs of transient ischemic attack.