|Graves, Donald -|
Submitted to: Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 1, 2011
Publication Date: January 27, 2012
Citation: Panickar, K.S., Polansky, M.M., Graves, D.J., Urban Jr, J.F., Anderson, R.A. 2012. A procyanidin type A trimer from cinnamon extract attenuates glial cell swelling and the reduction in glutamate uptake following ischemic injury in vitro. Neuroscience. 202:87-98. Interpretive Summary: This article describes the protective role of a purified dietary cinnamon polyphenol fraction in a cell culture model of ischemia/stroke. A major feature of cerebral ischemia is the swelling of cells that are responsible for the development of brain edema. Our results suggested that swelling of brain-derived glial cells, when deprived of oxygen and glucose, can be significantly prevented by a biochemically isolated dietary cinnamon polyphenol. Our data suggests that cinnamon polyphenols exert protective effects through improved function of mitochondria by reducing free radical mediated damage and by regulating intracellular calcium. This article should be useful for the general public as well as scientists who are interested in the mechanisms underlying how dietary polyphenols protect neural function, and should lead to follow up studies in animal models and eventually humans to determine if polyphenol enriched diets can improve human health.
Technical Abstract: Dietary polyphenols exert neuroprotective effects in ischemic injury. The protective effects of a procyanidin type A trimer (trimer 1) isolated from a water soluble cinnamon extract (CE) were investigated on key features of ischemic injury including cell swelling, increased free radical production, increased intracellular calcium ([Ca2+]i), mitochondrial dysfunction, and the reduction in glutamate uptake. Astrocyte swelling is a major component of cytotoxic brain edema in ischemia and may contribute to increased intracranial pressure, brain herniation, and additional ischemic injuries. C6 glial cell cultures were exposed to oxygen-glucose deprivation (OGD) for 5 hr and cell swelling was determined at 90 min after the end of OGD. OGD-induced increases in glial cell swelling were significantly blocked by trimer 1 but not by the major non-polyphenol fractions of CE including cinnamaldehyde and coumarin. Increased free radical production was also significantly reduced by trimer 1. Mitochondrial dysfunction is hypothesized to contribute to glial cell swelling. Depolarization of the inner mitochondrial membrane potential (''m) was assessed using a fluorescent dye (TMRE), and was significantly attenuated by trimer 1, as was OGD-induced increased [Ca2+]i. Taken together with our previous observation that blockers of [Ca2+]i reduced cell swelling, our results indicated that trimer 1 attenuated cell swelling by regulating [Ca2+]i. Trimer 1 also significantly attenuated the OGD-induced decrease in glutamate uptake. In addition, cyclosporin A, a blocker of the mitochondrial permeability pore (mPT), but not FK506 (that does not block the mPT), reduced the OGD-induced decline in glutamate uptake indicating a role of the mPT in such effects. Thus, the effects of trimer 1 in attenuating the reduction in glutamate uptake are likely mediated through the mPT.