Article Text

  1. T. Shimizu,
  2. S. S. Shinmei,
  3. D. G. Fujikawa
  1. UCLA School of Medicine, Los Angeles, CA, and VA Greater Los Angeles Healthcare System, Sepulveda, CA


Purpose Previous studies have suggested that seizure induces necrotic death of neurons. However, the exact mechanism of neuronal cell death following seizures is not completely understood. The purpose of this study was to determine if either caspase-9 or caspase-8, upstream cysteine proteases in the intrinsic mitochondrial and Fas death receptor extrinsic caspase-dependent pathways respectively, is activated following 3-h lithium-pilocarpine-induced status epilepticus (LPCSE). In addition, presence or absence of activation of the central downstream executioner caspase caspase-3 was examined.

Methods LPCSE lasting 3 h was induced in male Wister rats, which were allowed to recover for 6 or 24 h before perfusion-fixation. Neuronal death was then assessed by light microscopy with H&E stain, TUNEL stain, and stains using caspase-3, caspase-8, and caspase-9 antibodies.

Results Consistent with previous findings, H&E showed morphologically necrotic neurons. TUNEL staining showed TUNEL-positive nuclei in those rats with 3 h status epilepticus (SE) and 24 h recovery but not in 3 h SE and 6 h recovery. Immunoreactivity to caspase-3, caspase-8, and caspase-9 was negative in both groups.

Conclusion These results show that neurons undergo necrotic cell death following seizures and that this process is independent of caspase pathways.

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