Deciphering the role of metal and non-metals in the treatment of epilepsy.

Metals and non-metals have known to play a significant role in various physiological roles in the body including the central nervous system (CNS). The alterations in their concentration in the CNS leads to abnormalities in the normal functions which may lead to various neurological conditions including epilepsy. Manganese is a cofactor required for antioxidant enzymes such as Superoxide dismutase, Glutamine synthetase, etc. The accumulation of iron leads to formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which have the potential to cause ferroptosis, one of the reasons for epileptogenesis. Zinc has biphasic response, both neurotoxic and neuroprotective, based on concentration levels in the CNS. Selenium is a main element for selenoproteins which is responsible for the regulation of oxidative state and antioxidant defence mechanism. The reduction in the phosphorous levels in the CNS is widely observed after generalised tonic clonic seizures (GTC), which can be a potential diagnostic biomarker. Copper acts in the CNS in an identical manner, i.e., by blocking both AMPA mediated and GABA mediated neuronal transmission. Magnesium blocks calcium channels in the NMDA receptor and prevents glutamatergic transmission, thus inhibiting excitotoxicity. Lithium acts as a proconvulsive agent and is used in combination with pilocarpine to induce seizures. The identified potential of metals and non-metals in epilepsy can be utilised in order to devise new adjuvant therapies for the management of epilepsy. The article summaries in depth the role of metals and non-metals in the treatment of epilepsy supported with special paragraph on author perspective on to the topic. Furthermore, an update of preclinical and clinical evidences are discussed in the review to give evidence on metal and non-metal based therapies in epilepsy.

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Declaration of competing interest The authors declare no conflict of interest.