The Time Course and Circuit Mechanisms of Acquired Epileptogenesis

Excerpt

Identification of the critical molecular and cellular mechanisms that lead to acquired epilepsy depends on an understanding of the time course of the development of spontaneous recurrent seizures after a brain injury. Here, the temporal characteristics of acquired epilepsy were studied using nearly-continuous video-electrographic (EEG) recordings in (1) kainate-treated rats, a model of temporal lobe epilepsy, and (2) rats subjected to unilateral carotid occlusion with superimposed hypoxia at postnatal day 7, a model of perinatal stroke. The data do not support the hypothesis that epileptogenesis is a step function of time after injury; rather, epileptogenesis appears to be a continuous process that starts at the time of the brain injury and extends well past the first spontaneous clinical seizure. Histopathological and electrophysiological data strongly support two hypothetical mechanisms that are probably important for acquired epileptogenesis: (1) the selective loss of specific, vulnerable, GABAergic interneurons, and (2) axon sprouting and the progressive formation of new recurrent excitatory circuits. These circuit mechanisms may contribute to the latent period and the progressive increase in the frequency and severity of spontaneous recurrent seizures characteristic of acquired epilepsy, which may be an important consideration in the development of strategies to suppress epileptogenesis after brain injury.