STATUS EPILEPTICUS INDUCED DAMAGE AND MORTALITY IN SEVERAL STRAINS OF MICE.
Abstract number :
2.080
Submission category :
Year :
2003
Submission ID :
1961
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Jill R. Turner, Ananth Charya, Alexei Kondratyev, Karen Gale Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC; Department of Pharmacology, Georgetown University, Washington, DC; Department of Pediatrics, Georgetown Universi
Differences in susceptibility to neuronal damage as well as differences in seizure phenotype across inbred mouse strains have complicated the selection of appropriate models for studying status epilepticus (SE) induced damage in mice. Many of the genetically modified mouse models in current use involve the C57Bl/6 mouse as a background strain. However, it is difficult to induce forebrain seizures in this strain without evoking brainstem seizure manifestations and concomitant mortality. The present study was designed to determine whether alternative strains of mice are more suitable for the selective induction of limbic forebrain SE.
Kainic acid was administered i.p. in a dose of 30 mg/kg to groups of mice (n = 24 per group) of each of the following strains: C57Bl/6J, DBA/1J, FVB/NJ, and Balb/CJ. In half of each group, SE was terminated after 2 h by administration of diazepam (20 mg/kg i.p.). In the other half of each group, no diazepam was given. DNA fragmentation in hippocampus and entorhinal cortex was measured at 24 hrs and cupric silver degeneration staining was performed at 72 hours following SE.
Mortality was closely associated with brainstem seizure manifestations, including hindlimb clonus and running/bouncing. C57Bl/6J mice exhibited the highest mortality (50% lethality without diazepam, 100% lethality with diazepam), while the other 3 strains experienced not more than 25% mortality. Termination of seizures with diazepam did not significantly change mortality in DBA/1J, FVB/NJ, and Balb/CJ mouse strains. The surviving C57Bl/6J and Balb/CJ mice exhibited little or no DNA fragmentation, while the DBA/1J mice exhibited moderate fragmentation, but only in the subgroup that did not receive diazepam. The FVB/NJ mice all exhibited robust DNA fragmentation. Silver impregnation revealed that FVB/NJ mice sustained the greatest amount of cell death, whereas the least evidence of cell death was observed in C57Bl/6J and Balb/CJ mouse strains.
Our results confirm previous observations that C57Bl/6J mice are resistant to KA-induced neuronal injury. We have also demonstrated that FVB/NJ mice are susceptible to kainic acid induced apoptotic neuronal death, and exhibit relatively selective limbic SE and low mortality. Based on these findings, we suggest that the FVB/NJ mouse strain is particularly suitable for studies of SE induced cell death in the forebrain and is also appropriate for studies requiring long term survival.
[Supported by: NIH grants T32NS41231(JT), NS20576, and MH2040.]