Nicotinamide attenuates the injury-induced decrease of hippocalcin in ischemic brain injury

- Nicotinamide protects brain tissues against cerebral ischemic injury.
- Nicotinamide prevents brain injury-induced decrease of hippocalcin.
- Nicotinamide prevents glutamate exposure-induced decrease of hippocalcin in HT22 cells.

Nicotinamide is an important cofactor in the prevention of brain damage during focal cerebral ischemia. Hippocalcin is a calcium buffer protein that modulates intracellular calcium concentration and attenuates apoptosis. In this study, we investigated whether nicotinamide modulates hippocalcin expression during cerebral ischemia. Male Sprague-Dawley rats were treated with vehicle or nicotinamide (500 mg/kg) 2 h after the onset of middle cerebral artery occlusion (MCAO) and cerebral cortex tissues were collected 24 h after MCAO. Nicotinamide treatment decreased infarct volume in the cerebral cortex of MCAO-operated animals. Our proteomic approach revealed a decrease in hippocalcin expression in vehicle-treated animals during MCAO, which was attenuated by nicotinamide treatment. We used RT-PCR and Western blot analyses to demonstrate that nicotinamide clearly restored the injury-induced decrease in hippocalcin expression. Glutamate toxicity also decreased hippocalcin levels in cultured hippocampal cells, while nicotinamide treatment prevented the glutamate exposure-induced decrease in hippocalcin levels. These results suggest that nicotinamide modulates hippocalcin expression in cerebral ischemic injury and consequently contributes to the prevention of neuronal cell death.