Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. Previously, we demonstrated that the postictal period is marked by a long-lasting stroke-like event in both animal models and humans with epilepsy (Farrell et al., 2016). Here, we assessed potential mechanisms by which this vascular event leads to memory impairment by studying the hippocampus of rodent seizure models. While

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... uronal activity and local field oscillations were unchanged during the postictal state, memory and long-term potentiation of the temporoammonic pathway to CA1 were significantly impaired, but only when severe local hypoxia occurred. Prevention of postictal stroke-like events by cyclooxygenase inhibition rescued memory impairment and supports a necessary role of hypoperfusion/hypoxia in postictal amnesia. These results provide an objective pathophysiological criterion for defining the postictal state and identifies a strategy and potential drug candidates for treating it.