Mechanisms of focal and generalized spike-wave seizures.

Our research on epilepsy is targeted to discover the cellular and network mechanisms underlying the transformation of normal brain oscillations to electrographic seizures. The long-term goal of this research is to design approaches that could be further developed to treat humans with trauma-induced epilepsy in clinical settings.



Role of ion concentration dynamics in epileptogenesis and seizures

The role of intra- and extracellular changes in ion concentrations in epilepsy has remained unclear. Many types of seizure manifest themselves in stereotype patterns of electrical activity characterized by large amplitude periodic fluctuations of the local field potential (LFP), paroxysmal de-polarization shift (PDS), alternations of the spike/polyspike and wave (SW/PSW) EEG discharges and fast runs of EEG spikes. Multiple evidences suggest, however, that ionic concentrations may fluctuate significantly during seizure. Indeed, substantial fluctuations of extracellular K+ concentration were found during electrically- or pharmacologically-induced paroxysmal activity. Extracellular Ca2+ concentration reduces during epileptic seizures, thus decreasing reliability of synaptic transmis-sion and increasing intracellular excitability. Extracellular Na+ decreases during epileptiform activity, which likely corresponds to increase of intracellular sodium concentration. Depolarizing effects of GABAa receptor activation during seizure suggest elevated levels of intracellular Cl- concentration. The changes of the ion concentrations can have profound effects on the network dynamics and may be responsible for the characteristic patterns of electrical activity observed during seizures. The goal of our research is to explore the role of ionic dynamics in generation and termination of spike-wave seizures.


Trauma-induced epileptogenesis

Epileptogenesis following brain trauma may extend over weeks before spontaneous epileptic seizures occur. The goal of our research is to explore the changes of the traumatized brain network that lead to epileptogenesis and to reveal interventions that may prevent or reduce likelihood of seizures. We proposed and explore a hypothesis that homeostatic synaptic plasticity – a form of plasticity triggered by an increase or decrease of the overall level of excitation in a population of neurons and which normally maintains a moderate level of electrical activity in the cortex, may fail to control neuronal excitability in the pathological brain conditions found after brain trauma and may lead to development of epileptic seizures. Our studies involving different types of computer models and based on experimental data may not only explain the mechanisms underlying trauma-induced epileptogenesis, but also predict new clinical interventions (such as external stimulation of the traumatized area) to prevent epileptogenesis.