Abstracts

Rationale: Epilepsy is the most common serious neurological disease, affecting 1 in 140 of the UK population(1), and patients can experience psychological and biosociological symptoms, which may be due to seizure-induced cell dysfunction. Oxidative stress is a candidate mechanism for this(2). Isoprostanes are the product of the non-enzymatic oxidation of arachidonic acid, and are a marker of oxidative stress. They are increased in neurodegenerative conditions(3) where oxidative stress is known to be relevant, but they have been little studied in epilepsy to date. 8-iso-PGF_2α is raised across a broad range of neurodegenerative conditions, and is active physiologically, and for these reasons was selected as the isoprostane of choice for further study. Methods: All experiments followed the UK Animal (Scientific Procedures) Act, 1986. Self-sustaining status epilepticus was induced in adult male Sprague-Dawley rats using the perforant path model, and terminated with IP diazepam after 3 hours. 44 hours following cessation of seizures, the animals were decapitated and hippocampus dissected on ice. Using LC-MS, levels of 8-iso-PGF_2α were measured in hippocampus from status animals (n=8) and sham controls (n=6). Results were compared using the Mann Whitney test. Results: 8-iso-PGF_2α was increased in rat hippocampus in status animals (141.6 nmol/0.1g ± 21.63 SEM) compared with sham controls (76.52 nmol/0.1g ± 6.38 SEM), p=0.008. Conclusions: This study is proof of principle that isoprostanes are raised and can be measured following status epilepticus using an electrical model of seizures in freely moving rats. This sheds further light on the pathophysiological consequences of seizures, and may help us to understand the mechanisms by which seizures can change neuronal or glial function, or cause cell death. They might also serve as a biomarker to monitor the effects of seizures, and potentially to identify patients at high risk of the non-seizure symptoms of epilepsy. Further work is necessary to confirm these findings, clarify the time course of the observed changes, and identify the molecular and cellular consequences, with the eventual aim of developing urgently required novel, possibly neuroprotective, treatments for epilepsy.