Grant: Operating Grant

Immediate response to brain damage is a generation of seizure activities. These seizures are reasonably well controlled by drugs and if untreated they terminate within days. Thereafter the patient recovers (at least in terms of seizures). However, months or years after penetrating brain wounds occur, about 70% of patients develop epilepsy characterized by spontaneous generation of unprovoked seizures. These seizures are not well controlled by drugs. The process between brain damage and onset of epilepsy is called epileptogenesis. The mechanisms of epileptogenesis are largely unknown and therefore, there are no effective therapies against epileptogenesis. Prevention of epileptogenesis will prevent epilepsy. We obtained preliminary data showing that in adult but not young cats and mice penetrating cortical wounds lead to development of epilepsy. How epileptogenesis happens: hypothesis? The normal brain has some level of excitability, which is a balance of excitation and inhibition. Brain damage reduces mainly excitatory influences. Homeostatic plasticity mechanisms up-regulate network excitability to bring it to initial level. That what is happening in young animals. In adult animals the same up-regulation of excitability occurs, but it does not stop when a sufficient level of excitability reached and therefore, it brings network to hyperexcitable state - epilepsy. What do we want to do? Basically two things: (1) To describe physiological processes taking place during epileptogenesis and (2) Based on understanding of changes in network activity and starting from the moment of trauma to stimulate traumatized cortex aiming to increase excitability and to prevent epileptogenesis.