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DOI: 10.14704/nq.2017.15.1.1014

A Bio-Electrical Tornado in The Hippocampus: Mechanisms of Temporal Lobe Epilepsy

Umit H Sayin

Abstract


This review summarizes the structural and electrophysiological changes in the epileptic hippocampus in various animal models of epilepsy. Tornado hypothesis of epileptic hippocampus, states that there are many progressive detrimental changes in the hippocampus of the epileptic rats. PTZ, PTZ kindling, pilocarpine, electrical kindling, kainic acid, hyperthermia and in vitro models are taken as primary animal epilepsy models in this review. Paired pulse inhibition and GABAergic transmission is decreased in dentate gyrus (DG), CA3 and CA1 regions of the epileptic hippocampus. There is interneuron loss in the hilus, DG and CA3, while excitatory input from perforant path (PP) is increased and this is fed into the CA3 area by mossy fibers (MF) which have excessive sprouting that forms novel recurrent synapses with the pyramidal cells of CA3. Gate function of DG is either impaired or lost. CA3 area of hippocampus becomes an epileptic focus and sends ictal discharges. These ictal discharges are carried into CA1 by Schaffer collaterals and then into entorhinal cortex (EC). The input from EC is amplified in the hippocampal circuitry which is fed into hippocampus from EC into DG again successively. Thus a weak electrical input into the hippocampal formation results in an amplified signal back into EC. Since the basic ultrastructural and electrophysiological feed-back control mechanisms are impaired, this electrical tornado cannot be compensated for and an epileptic amplified ictal discharge spreads to the limbic system and other adjacent structures of the brain. Eventually the hippocampal circuitry, that has developed a vicious circle, becomes a bio-electrical amplifier which triggers an electrical tornado, under certain bio-chemical conditions.

Keywords


Animal models of epilepsy; tornado hypothesis of epilepsy; CA3; CA1; Dentate gyrus; PPI; kindling; kainic acid; PTZ; epileptic hippocampus; pilocarpine; febrile convulsion; GABAergic inhibition; interneuron; mossy fiber sprouting; in vitro

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References


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Supporting Agencies

NIH, Veterans Administration, Epilepsy Foundation, İstanbul University



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