Ferulic acid prevents cerebral ischemic injury‐induced reduction of hippocalcin expression

Intracellular calcium overload is a critical pathophysiological factor in ischemic injury. Hippocalcin is a neuronal calcium sensor protein that buffers intracellular calcium levels and protects cells from apoptotic stimuli. Ferulic acid exerts a neuroprotective effect in cerebral ischemia through its anti‐oxidant and anti‐inflammation activity. This study investigated whether ferulic acid contributes to hippocalcin expression during cerebral ischemia and glutamate exposure‐induced neuronal cell death. Rats were immediately treated with vehicle or ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brain tissues were collected 24 h after MCAO and followed by assessment of cerebral infarct. Ferulic acid reduced MCAO‐induced infarct regions. A proteomics approach elucidated a decrease in hippocalcin in MCAO‐operated animals, ferulic acid attenuates the injury‐induced decrease in hippocalcin expression. Reverse transcription‐polymerase chain reaction and Western blot analyses confirmed that ferulic acid prevents the injury‐induced decrease in hippocalcin. In cultured HT22 hippocampal cells, glutamate exposure increased the intracellular Ca 2+ levels, whereas ferulic acid attenuated this increase. Moreover, ferulic acid attenuated the glutamate toxicity‐induced decrease in hippocalcin expression. These findings can suggest the possibility that ferulic acid exerts a neuroprotective effect through modulating hippocalcine expression and regulating intracellular calcium levels. Synapse 67:390–398, 2013. © 2013 Wiley Periodicals, Inc.