Stress is widely recognized as a precipitating factor for seizures in many patients with epilepsy 
. Despite a clear correlation between stress and seizures such that many patients are able to predict their own seizures with great accuracy 
, whether a causal relationship between stress and epilepsy exists is not known. Indeed, changes in the brain preceding a seizure might increase patient perceptions of stress and anxiety rather than the converse. Alternatively, factors related to stress, such as sleep loss, rather than stress per se
may account for the correlation. Nonetheless, understanding the relationship between stress and seizures is important. Chronic stress can lead to lasting changes in brain structure and function 
, providing a possible mechanism by which stress might impact epilepsy. For example, in the hippocampus – a brain region implicated in temporal lobe epilepsy – stress alters dentate granule cell proliferation 
and regulates dendritic and synaptic plasticity 
. Therefore, it is conceivable that stressful events could increase the likelihood that at-risk individuals will develop epilepsy, or worsen the course of the disease in patients with pre-existing epilepsy. Identifying such “disease-modifying” effects of stress on epilepsy could be extremely important for clinical management of the disorder.
Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, leading to the release of a variety of neuropeptides and hormones 
. Glucocorticoids – corticosterone (CORT) in rodents and cortisol in humans – are prominent among these. CORT exerts its effects through high-affinity mineralocorticoid receptors and comparatively lower affinity glucocorticoid receptors. Both receptors act by binding DNA response elements to alter gene expression, and are thus capable of producing relatively slow developing but long-lasting changes in transcription. In addition, glucocorticoids can also act through non-genomic mechanisms, leading to more rapid changes in behavior and physiology 
. Both receptor types are expressed at high levels in cortex and hippocampus 
and act to regulate the excitability of cortical and hippocampal neurons 
Although the mechanisms underlying epileptogenesis are still being elucidated, it is clear that many patients' seizures originate from discrete brain regions. These brain regions often exhibit damage from injury (e.g. hypoxia, status epilepticus), tumors or developmental defects (e.g. heterotopias), and are commonly found in the cortex or temporal lobe. Surgical removal of these damaged regions is highly effective at controlling seizures 
, providing compelling evidence that these regions originate the seizures. Evidence for disease-causing brain lesions in patients with epilepsy, however, fails to explain the paroxysmal nature of the disorder. To restate the question, why should epileptic foci, which are always present, only occasionally provoke seizures? The implication is that most of the time, the balance between excitation and inhibition in the brain is adequately maintained such that despite the presence of an epileptic focus, seizures do not occur. Changes in factors which can alter excitation and inhibition in brain presumably upset this balance sporadically, provoking seizures. The present study explores whether CORT could be one of those factors.
To determine whether increasing CORT levels in animals with pre-existing epilepsy would provoke seizures, we treated epileptic mice with exogenous CORT while monitoring ictal and interictal EEG activity. Animals were rendered epileptic using the pilocarpine-status epilepticus model of epilepsy.