Distinct spatial and temporal activation of caspase pathways in neurons and glial cells after excitotoxic damage to the immature rat brain

Sonia Villapol, Laia Acarin, Maryam Faiz, Bernardo Castellano, Berta Gonzalez

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17 Scopus citations


Although cleaved caspase-3 is known to be involved in apoptotic cell death mechanisms in neurons, it can also be involved in a nonapoptotic role in astrocytes after postnatal excitotoxic injury. Here we evaluate participation of upstream pathways activating caspase-3 in neurons and glial cells, by studying the intrinsic pathway via caspase-9, the extrinsic pathway via caspase-8, and activation of the p53-dependent pathway. N-methyl-D-aspartate (NMDA) was injected intracortically in 9-day-old postnatal rats, which were sacrificed at several survival times between 4 hr postlesion (pl) and 7 days pl. We analyzed temporal and spatial expression of caspase-8, caspase-9, and p53 and correlation with neuronal and glial markers and caspase-3 activation. Caspase-9 was significantly activated at 10 hpl, strongly correlating with caspase-3. It was present mainly in damaged cortical and hippocampal neurons but was also seen in astrocytes and oligodendrocytes in layer VI and corpus callosum (cc). Caspase-8 showed a diminished correlation with caspase-3. It was present in cortical neurons at 10-72 hpl, showing layer specificity, and also in astroglial and microglial nuclei, mainly in layer VI and cc. p53 Expression increased at 10-72 hpl but did not correlate with caspase-3. p53 Was seen in neurons of the degenerating cortex and in some astrocytes and microglial cells of layer VI and cc. In conclusion, after neonatal excitotoxicity, mainly the mitochondrial intrinsic pathway mediates neuronal caspase-3 and cell death. In astrocytes, caspase-3 is not widely correlated with caspase-8, caspase-9, or p53, except in layer VI-cc astrocytes, where activation of upstream cascades occurs.

Original languageEnglish (US)
Pages (from-to)3545-56
Number of pages12
JournalJournal of Neuroscience Research
Issue number16
StatePublished - Dec 2007


  • Animals
  • Apoptosis
  • Brain
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases
  • Enzyme Activation
  • Female
  • Gliosis
  • Male
  • Nerve Degeneration
  • Neuroglia
  • Neurons
  • Neurotoxins
  • Rats
  • Rats, Long-Evans
  • Signal Transduction
  • Time Factors
  • Tumor Suppressor Protein p53
  • Journal Article
  • Research Support, Non-U.S. Gov't


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