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

摘要: Although cleaved caspase-3 is known to be involved in apoptotic cell death mechanisms neurons, it can also a nonapoptotic role astrocytes after postnatal excitotoxic injury. Here we evaluate participation of upstream pathways activating neurons and glial cells, by studying the intrinsic pathway via caspase-9, extrinsic caspase-8, activation p53-dependent pathway. N-methyl-D-aspartate (NMDA) was injected intracortically 9-day-old rats, which were sacrificed at several survival times between 4 hr postlesion (pl) 7 days pl. We analyzed temporal spatial expression p53 correlation with neuronal markers activation. Caspase-9 significantly activated 10 hpl, strongly correlating caspase-3. It present mainly damaged cortical hippocampal but seen oligodendrocytes layer VI corpus callosum (cc). Caspase-8 showed diminished 10–72 showing specificity, astroglial microglial nuclei, cc. Expression increased hpl did not correlate Was degenerating cortex some cells In conclusion, neonatal excitotoxicity, mitochondrial mediates death. astrocytes, widely correlated or p53, except VI-cc where cascades occurs. © 2007 Wiley-Liss, Inc.