Development of a model of seizure-induced hippocampal injury with features of programmed cell death in the BALB/c mouse.
Although mice are amenable to gene knockout, they have not been exploited in the setting of seizure-induced neurodegeneration due to the resistance to injury of key mouse strains. We refined and developed models of seizure-induced neuronal death in the C57BL/6 and BALB/c strains by focally evoking seizures using intra-amygdala kainic acid. Seizures in adult male BALB/c mice, or C57BL/6 mice as reference, caused ipsilateral death of CA1 and CA3 neurons within the hippocampus. Termination of seizures by lorazepam was more effective than diazepam in both strains, largely restricting neuronal loss to the CA3 sector. Electroencephalography (EEG) recordings defined injurious and non-injurious seizure patterns, which could not be separated adequately by behavioral observation alone. Degenerating neurons in the hippocampus were positive for DNA fragmentation and approximately a third of these exhibited morphologic features of programmed cell death. Western blot analysis revealed the cleavage of caspase-8 after seizures in both strains. These data refine our C57BL/6 model and establish a companion model of focally evoked limbic seizures in the BALB/c mouse that provides further evidence for activation of programmed cell death after seizures.
Shinoda
Sachiko
S
Robert S Dow Neurobiology laboratories, Legacy Research, Portland, Oregon 97232, USA.
Araki
Tomohiro
T
Lan
Jing-Quan
JQ
Schindler
Clara K
CK
Simon
Roger P
RP
Taki
Waro
W
Henshall
David C
DC
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008140:Lorazepam / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009474:Neurons / Q000473:pathology; D012640:Seizures / Q000473:pathology*
D000927:Anticonvulsants; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases; D008140:Lorazepam; D003975:Diazepam