Abstracts

Sublethal brain insults can confer protection against cell death induced by subsequent (prolonged) damaging insults. While best described for ischemia, there is some evidence brief seizures may precondition the brain against damage following prolonged seizures (e.g. [italic]status epilepticus[/italic]). To study this so-called [ldquo]epileptic tolerance[rdquo], we examined neuronal damage following [italic]status epilepticus[/italic] in mice that received various doses of sublethal preconditioning seizures and at various intervals between the conditioning and injurious stimuli., Seizure preconditioning activity was induced by intra-peritoneal (i.p.) injection of kainic acid (KA) at various doses (5.0, 7.5 and 15.0 mg/kg; [italic]n[/italic] = 5, plus vehicle controls, [italic]n[/italic] = 9) and subsequent [italic]status epilepticus[/italic] was induced by intra-amygdala (i.a.) injection of KA (1.0 ug) at two time-points (24 or 72 hours) after the first insult. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and NeuN immunostaining was used to detect neuronal damage within the hippocampus., Preconditioning seizures did not induce significant hippocampal damage at any dose tested. Mice that received preconditioning seizures induced by KA i.p. at 15.0 mg/kg given 24 hours before i.a. KA showed significant reductions in TUNEL counts and significantly more surviving neurons as assessed by NeuN in the ipsilateral hippocampus, particularly the CA3 subfield ([italic]p[lt][/italic]0.01). There were no significant differences in the duration of high amplitude polyspike seizures evoked by i.a. KA in mice that received preconditioning. Surprisingly, increasing the time interval between preconditioning and prolonged seizures to 3 days resulted in raised mortality rates (e.g. 3/5) when mice underwent the second prolonged (i.a. KA) seizures: evidence of preconditioning-induced sensitization to seizures., This study provides a new model with which to investigate the molecular mechanisms underlying endogenous neuroprotection programmes in brain., (Supported by Science Foundation Ireland grant B466.)