Epilepsy is believed to be largely associated with the mental dysfunction. It was considered as a scary disease in the ancient writings and the term has been derived from the Greek word meaning 'to seize upon'. It was first described by Hughlings Jackson in the nineteenth century as an intermittent derangement of the nervous system due to a sudden, excessive disorderly activity of a group or groups of cerebral neurons. An epileptic neuron is a hyperexcitable cell i.e., a cell which has acquired a tendency to produce electrical discharges considerably higher than the normal. Epileptic seizures may result either from excessive excitation or from a reduced inhibition of a group of epileptic neurons. In animal model, post-traumatic epilepsy (PTE) can be induced by ferrous or ferric chloride injection. Intracortical injection of iron salt solution in the rat has been found to produce acute and chronic epileptic bursts, which has been shown to last for three months or more. Subsequently, electrophysiological findings have contributed to the understanding of the initial features of iron-induced epilepsy.
Curcumin is 1,-bis (4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a major component of the rhizome of Curcuma longa (turmeric) commonly used as a food flavoring spice in many countries. It is a yellow substance; polyphenolic compound derived from the roots and is known for a large number of beneficial capabilities. It is an orange-yellow crystalline powder practically insoluble in water.
It is also known as diferuloylmethane, and has been shown by many workers to have several pharmacological effects like anti-inflammatory, anti-nephrotoxic, anti-tumor, anti-mutagenic, anti-viral, anti-atherosclerotic etc. Furthermore, curcumin has also been widely documented as a chemopreventive agent in variety of cancers namely oral, forestomach, duodenal, colon, skin cancer, etc., both in humans as well as rats. In addition, certain reports on suppression of nitric oxide oxidation, vasodilation, hydrogen peroxide induced oxidative stress, immunomodulation and cholesterol excretion, indicates the beneficial effects of curcumin.
Role of curcumin in PTE
Following head trauma, many biochemical, physiological and structural changes occur in the brain, which may account for epileptogenesis. The extravasation of blood, flowed by haemolysis and deposition of haem containing compounds into the neuropil initiates a sequence of univalent redox reactions, generate free radical species, including superoxides, hydroxyl radicals, peroxides and perferryl ion and suggested that the interaction of these free radicals with neural membranes may render the latter hyperexcitable i.e., epileptogenic. These lyse red blood cells also affect normal synaptic transmission in the ferric chloride model of epilepsy in rats. Reports have also suggested that iron haemorrhage induces neuronal lipid peroxidation and excititoxicity, which could also account for post traumatic epilepsy. The epileptogenic potential of ferric chloride is due to oxidative stress generation, finally leading to neuronal cell death.
In light of the above statements, it can be said that post traumatic epileptogenesis is closely associated with the generation of oxidative stress (reactive oxygen and nitrogen species). Moreover, the currently available anti-epileptic drugs are associated with a large number of potential side-effects on cognitive and behavioral aspects of patients with traumatic head injury. Thus, it is assumed that the antioxidant treatment can prove beneficial in inhibiting epileptic seizures without any side-effects. With this idea, curcumin was also tested for its anti-epileptic therapeutic efficacy. Curcumin effectively inhibited the development of higher-grade seizures in experimental rats probably because of its iron chelating property. It also improved the memory and learning as demonstrated through behavioral experiments. Curcumin showed its anti-epileptic potential through suppression of lipid peroxidation, protein oxidation, protein kinase C activity and augmentation of Na+K+-ATPase activity.
In conclusion, the role of curcumin as an antioxidant, in the prevention and suppression of post-traumatic epileptic seizures has been widely acknowledged, as a consequence of this, the same could be considered as a potential anti-epileptogenic therapy for epilepsies caused by traumatic brain injury. However, the precise mechanism underlying its effect, safety and efficacy is still a major question of potential research.
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