Handbook of Vitamin C Research

300Mustafa NazıroğluKeywords: Vitamin C, ascorbate, calcium ions, non-antioxidant, oxidative stress, brain,neurodegeneration, epilepsy.List of AbbreviationsADPRADP-RiboseCNScentral nervous systemCSFcerobrospinal fluidMDAmalondialdehydeNMDA N-methyl-D-aspartatePARP-1 polyADP-ribose polymerase 1PTZpentylentetrazoleROSreactive oxygen speciesSODsuperoxide dismutaseTBARS thiobarbituric acid reactive substancesTRPM2 transient potential melastatin 2IntroductionEpilepsies are chronic dynamic significant medical problems. Some types of epilepsy,such as status epilepticus, have a mortality rate of 10–12%. The development of epilepsy is aplastic-adaptive process. This condition is characterized by prolonged or repetitive epilepticdischarges resulting in persistent clinical alterations of normal brain function and cognitivestate. Recent studies suggest that seizures can be associated with oxidative stress [1,2]. Freeradical generation can induce seizure activity by direct activation of glutamine synthatase,thereby permitting an abnormal buildup of excitatory neurotransmitter glutamic acid. Theonset of oxygen-induced convulsions in epileptic patients and animals is correlated with adecrease in the cerebral content of GABA, the neurotransmitter, because of the inhibition ofthe enzyme glutamate decarboxylase by reactive oxygen species (ROS). If ROS are notcontrolled by the enzymatic and nonenzymatic antioxidants, they can cause oxidative injury,i.e., peroxidation of cell membrane phospholipids, proteins (receptor and enzymes) and DNA.The brain is extremely susceptible to oxidative damage induced by these ROS because itgenerates extremely high levels of ROS due to its very high aerobic metabolism and bloodperfusion, and it has a relatively poor enzymatic antioxidant defense [3]. The brain containspolyunsaturated fatty acids which can readily be peroxidized [4]. Lipid peroxidation causesinjury to cells and intracellular membranes and may lead to cell destruction and subsequentlycell dead. Brains are protected by antioxidants from peroxidative damage [5]. It has beensuggested that ascorbic acid has neuroprotective properties in some experimental models ofseizure activity induced by various agents such as iron, methylmalonic acid andpentylentetrazole (PTZ) [6]. Ascorbate, the anionic form of L-ascorbic acid, is a watersolubleantioxidant vitamin that is found throughout the body and is highly concentrated inthe brain. Vitamin C—ascorbic acid, or ascorbate—has also many functions in the brain and