Abstracts

Rationale: Generalized periodic discharges (GPDs) can be observed in the EEG of patients after acute cerebral ischemia and reflect pathological neuronal synchronization. It is unclear which pathophysiological processes lead to the generation of GPDs. Whether GPDs represent ictal activity, which can be treated with anti-epileptic drugs, or severe ischemic damage, in which treatment is futile, is also unknown. We hypothesize that GPDs result from selective ischemic damage of glutamatergic synapses, which are known to be relatively vulnerable to effects of ischemia.Methods: We employed an established macroscopic model (Figure 1) (Liley, Network 2002) of cortical dynamics in which we increasingly eliminated glutamatergic synapses. We compared the output of the model with clinical EEG registrations showing GPDs of eight patients after acute cerebral ischemia due to cardiac arrest.Results: Selective elimination of glutamatergic synapses from pyramidal cells to inhibitory interneurons led to simulated GPDs whose wave shape and frequency matched those of patients after acute cerebral ischemia (Figure 2). Further reduction of the number of glutamatergic synapses from pyramidal cells to inhibitory interneurons rapidly resulted in complete depression of simulated cortical activity. Mere reduction of glutamatergic synapses between pyramidal cells themselves did not result in GPDs.Conclusions: Selective ischemic damage of glutamatergic synapses on inhibitory cortical interneurons probably plays a role in the generation of ischemia induced GPDs. Disinhibition of cortical pyramidal neurons is the likely mechanism.