Submitted to: Society for Neuroscience Abstracts and Proceedings
Publication Type: Proceedings
Publication Acceptance Date: July 15, 2009
Publication Date: October 15, 2009
Citation: Panickar, K.S., Polansky, M.M., Anderson, R.A. 2009. Myricetin and quercetin attenuate ischemic injury in glial cultures by different mechanisms. Society for Neuroscience Abstracts and Proceedings. Technical Abstract: We have demonstrated that polyphenols from cinnamon and green tea reduce cell swelling and mitochondrial dysfunction in C6 glial cultures following ischemic injury. We tested the protective effects of the flavonoid polyphenols, myricetin and quercetin, on key features of ischemic injury. C6 cultures were exposed to oxygen-glucose deprivation (OGD) for 5hr and cell swelling was determined 90 min after the end of OGD using the 3-O-methyl-glucose method. The OGD-induced increase in glial swelling was significantly blocked by both quercetin and myricetin. Increased free radical production, a contributing factor in cell swelling following ischemic injury, was also significantly reduced by myricetin and quercetin. OGD-induced decline in mitochondrial membrane potential was significantly attenuated by myricetin but not quercetin. An important feature of glial cells is maintenance of extracellular glutamate levels. Reduced glutamate uptake after ischemia is an important mechanism that can lead to excitotoxic damage. Myricetin, but not quercetin, attenuated the OGD-induced decrease in glutamate uptake. Additionally, cyclosporin A, a blocker of the mitochondrial permeability transition pore, but not FK506, attenuated the decline in glutamate uptake after OGD. Our results indicate that while both flavonoids significantly attenuate free radical production and cell swelling following ischemic injury, they likely employ different intracellular mechanisms to exert their effects. In addition, the differential effect of myricetin and quercetin on OGD-induced reduction in glutamate uptake may be due to their differential effects on mitochondria.