Abstracts

Rationale: Cerebrovascular disease is the most often identified cause of acquired epilepsies accounting for 11% of cases. Until recently, only a few studies focused on characterizing and understanding the mechanisms of epileptogenesis in ischemia models. The hippocampal formation is one of the brain regions most sensitive to ischemic damage. However, there are no studies about changes in hippocampal neuronal activity during and after a selective unilateral hippocampal ischemia and the role of the ischemic hippocampus in epileptogenesis. The use of anesthetics during stroke induction, which by themselves are neuroprotective and antiepileptic, also complicates the interpretation of data resulting from current animal models of poststroke epileptogenesis. The aim of this project was to develop a new stroke model in freely moving mice in order to avoid the use of anesthetics and to investigate the role of the postischemic hippocampus in epileptogenesis. Methods: We developed a novel unilateral cerebrovascular ischemia model in freely moving mice that selectively shuts down blood supply to the ipsilateral hippocampal formation. In the first step we implanted electrodes into both hippocampi of the mouse and a cannula guide just above the longitudinal hippocampal artery. After 10 days of recovery period an injection of Bengal Rose was given to the mouse and an optical fiber was inserted into the cannula guide. The Bengal Rose was activated in the freely moving mouse by illuminating (532 nm, green laser) the longitudinal hippocampal artery through the optical fiber. The photoactivated Bengal Rose occluded the artery resulting in a selective hippocampal stroke. Results: Local field potential recordings in the CA1 region of the hippocampus prior, during and after the induction of ischemia demonstrated a high frequency discharge reaching frequencies of over 300 Hz and lasting 10-30 s (n=5) during the illumination consistent with a massive synchronous neuronal activity. The high frequency discharge was invariably followed by a prominent step-like decrease at the low gamma frequencies (30-57 Hz). This decrease in gamma activity lasted for the entire duration of the recordings (~2 weeks) following ischemia. The contralateral hippocampus displayed high frequency discharges without long-lasting decreases in gamma oscillations.Conclusions: Our findings reveal for the first time the acute and chronic effects of unilateral hippocampal ischemia on ensemble hippocampal neuronal activities in freely moving mice, and may further uncover local field potential activity required for the induction of post-stroke epilepsy.