Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisation

Neurochem Int. 2003 Aug;43(3):211-23. doi: 10.1016/s0197-0186(03)00002-0.


The relationship between caspase-3 activation and delayed neuronal death after ischemia was examined. Expression of caspase-3 was evaluated by colorimetric assay, immunoblotting and by immunohistochemistry. Apoptosis was characterised by terminal desoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labelling. Immunohistochemistry showed caspase-3 activation in the whole hippocampus as early as 30 min after ischemia with exclusive localisation in fiber systems, especially in the perforant path and mossy fibers, Schaffer-collaterals, as well as apical and basal dendrites of pyramidal cells. One day post-ischemia, the 18 kDa cleavage product of caspase-3 (p18) was seen in all cell compartments (nucleus, cytosol and dendrites) throughout the entire subfields and the dentate gyrus with high distribution in mossy fibers. Two days post-ischemia, p18 kDa was only seen in the nuclei and cytosol of hippocampal cells without specific regional differences among hippocampal subfields. A significant number of apoptotic cells appeared only in the CA1 pyramidal cells at 2-3 days post-ischemia. Our data provides the first evidence that caspase-3 activation was detectable in the trisynaptic pathway fiber bundles which probably correspond to perforant path, alvear path and collaterals of Schaffer, and that activation of caspase-3 led to execution of apoptotic cell death program in selectively vulnerable areas, but not in the resistant area of the hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / enzymology*
  • Blotting, Western
  • Brain Ischemia / enzymology*
  • Caspase 3
  • Caspases / metabolism*
  • Colorimetry
  • Dendrites / enzymology*
  • Enzyme Activation
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Rats
  • Rats, Wistar


  • Casp3 protein, rat
  • Caspase 3
  • Caspases