Abstract
Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (Nos. 81371318 and 81100873), Young Scientists Project of Health Department of HuBei Province, China (No. QJX2010-27), Natural Science Foundation of Yichang City, HuBei Province, China (No. A01301-02), CTGU Graduate Innovation and Creativity Funds (No. 2012CX057), Training Program for Outstanding Young Medical Talents in Shanghai Pudong New District Health System (No. PWRq2010-05), the Fundamental Research Funds for the Central Universities (No. 2011KJ008).
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Zhi He and Min Hu contributed equally to the paper.
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He, Z., Hu, M., Zha, Yh. et al. Piracetam Ameliorated Oxygen and Glucose Deprivation-Induced Injury in Rat Cortical Neurons Via Inhibition of Oxidative Stress, Excitatory Amino Acids Release and P53/Bax. Cell Mol Neurobiol 34, 539–547 (2014). https://doi.org/10.1007/s10571-014-0037-x
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DOI: https://doi.org/10.1007/s10571-014-0037-x