Hippocampal damage after intra-amygdala kainic acid-induced status epilepticus and seizure preconditioning-mediated neuroprotection in SJL mice.
Exposure of the brain to a stressful stimulus that is sub-threshold for permanent injury can temporarily protect against cell death during a subsequent and otherwise damaging insult. One or more brief, non-harmful seizure episode(s) (seizure preconditioning) can dramatically reduce hippocampal damage when given prior to status epilepticus (epileptic tolerance). We recently reported that status epilepticus-induced hippocampal damage in C57BL/6 mice could be reduced by approximately 50% when preceded 24h earlier by a brief, non-injurious generalized seizure induced by 15mg/kg systemic kainic acid (KA). Since other mouse strains might display different vulnerability to either seizure preconditioning or status epilepticus, we investigated whether epileptic tolerance could be acquired in another strain. SJL mice, reported to display greater seizure sensitivity to systemic KA, received intra-amygdala microinjection of KA to trigger status epilepticus. Intracerebral recordings confirmed evoked seizures involved the ipsilateral hippocampus. Status epilepticus produced hippocampal damage which mainly affected the ipsilateral CA3 and hilus; a pattern similar to C57BL/6 mice. The damage extended through the full rostro-caudal extent of the hippocampal formation. Seizure preconditioning using 20mg/kg systemic KA, but not 15mg/kg, significantly reduced hippocampal damage after status epilepticus by 37% in the dorsal hippocampus and by 65% in the ventral hippocampus. These studies suggest status epilepticus induced by intra-amygdala KA in SJL mice models aspects of the pathophysiology of human mesial temporal sclerosis. Moreover, seizure preconditioning effectively produces neuroprotection in SJL mice, further establishing epileptic tolerance as a conserved endogenous neuroprotection paradigm.
Tanaka
Katsuhiro
K
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Jimenez-Mateos
Eva M
EM
Matsushima
Satoshi
S
Taki
Waro
W
Henshall
David C
DC
D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000502:physiology*; D004567:Electrodes, Implanted; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D007608:Kainic Acid; D051379:Mice; D008845:Microinjections; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents; D012598:Sclerosis / Q000473:pathology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology
D018696:Neuroprotective Agents; D007608:Kainic Acid