Abstracts

Rationale: Uncontrolled epileptic seizure causes excessive free radical production of reactive oxygen species (ROS), leading to cell death and subsequent epileptogenesis. Hippocampus, the most vulnerable region to seizure-induced oxidative stress, has a differential susceptibility according to its subfields: most vulnerable in CA1, CA3, and hilus, but resistant in dentate gyrus (DG). The exact reason remains obscure. We examined the relation between the neuronal death and anti-oxidant defense capacity in each hippocampal subfield after status epilepticus (SE). Methods: Adult male C57BL/6J mice were pre-treated with scopolamine (1 mg/kg, i.p.), and given injections of pilocarpine (325 mg/kg, i.p.) 30 min thereafter. Hippocampal neuronal death was assessed by cresyl-violet staining. The temporal and spatial distribution of hippocampal ROS was investigated using in situ detection of oxidized hydroethidine (HEt), administered intravenously through jugular vein 1 h before sacrifice, then observed under fluorescent microscope and analyzed semi-quantatively. Superoxide dismutase 1 (SOD1) level was analyzed using a specific antibody, and compared between the normal and epileptic hippocampal subfields. Results: Cell death after SE was much prominent in subfield CA1, CA3, and hilus, but less in DG and CA2. HEt level, expressed by immunofluorescent analysis, was higher than control 1 day after SE in each subfield; however, the HEt level was significantly decreased in subfield DG and CA2 at 3 days after SE, that was sharply contrasted with more increased HEt level in subfield CA1, CA3, and hilus. SOD1 level was significantly decreased in CA3 and hilus compared to control, remained similar level in CA1, but significantly increased in CA2 and DG subfields. Conclusions: Differential vulnerability of hippocampus after SE was in line with increased free radical level by ROS in each hippocampal subfield. The differential expression of SOD1 in each subfield may suggest that the defense mechanism against oxidative stress might play a pivotal role in protection against hippocampal neuronal death after SE.