Stress-induced bystander signaling as a possible factor contributing to neuronal excitability and seizure generation/epileptogenesis.

We hypothesize that cell stress-caused bystander signaling induced by certain exogenous and endogenous stressors, such as ionizing radiation exposure, chemicals, tumor, or senescent cells, might contribute to neuronal excitability and synchronization, specifically to initiation of hyperexcitability, excessive synchronization and seizure generation in epileptic brain/epileptogenesis. It is suggested that bystanderly induced interconnected variations in cytosolic Ca(2+), cytokines, and reactive oxygen/nitrogen species, and in activity of mitogen-activated protein kinases and nuclear factor κB pathways might affect neurotransmitter system, neuronal receptors and ion channels implicated in seizure generation/epileptogenesis, or modulate expression of genes associated with epileptogenesis. The mechanism suggested may, at least partly, explain the emerging evidence of association between exposures to low-dose ionizing radiation and epileptogenesis. The bystander mechanism for the generation of epilepsy might constitute new potential molecular target for the design of antiepileptic drugs.