Temporal profile and cell subtype distribution of activated caspase-3 following experimental traumatic brain injury

This study investigated the temporal expression and cell subtype distributi on of activated caspase-3 following cortical impact-induced traumatic brain injury in rats. The animals were killed and examined for protein expressio n of the proteolytically active subunit of caspase-3, p18, at intervals fro m 6 h to 14 days after injury. In addition, we also investigated the effect of caspase-3 activation on proteolysis of the cytoskeletal protein alpha-s pectrin. Increased protein levels of p18 and the caspase-3-specific 120-kDa breakdown product to alpha-spectrin were seen in the cortex ipsilateral to the injury site from 6 to 72 h after the trauma. Immunohistological examin ations revealed increased expression of p18 in neurons, astrocytes, and oli godendrocytes from 6 to 72 h following impact injury, In contrast, no evide nce of caspase-3 activation was seen in microglia at all time points invest igated. Quantitative analysis of caspase-3-positive cells revealed that the number of caspase-3-positive neurons exceeded the number of caspase-3-posi tive glia cells from 6 to 72 h after injury. Moreover, concurrent assessmen t of nuclear histopathology using hematoxylin identified p18-immunopositive cells exhibiting apoptotic-like morphological profiles in the cortex ipsil ateral to the injury site. In contrast, no evidence of increased p18 expres sion or alpha-spectrin proteolysis was seen in the ipsilateral hippocampus, contralateral cortex, or hippocampus up to 14 days after the impact. Our r esults are the first to demonstrate the concurrent expression of activated caspase-3 in different CNS cells after traumatic brain injury in the rat. O ur findings also suggest a contributory role of activated caspase-3 in neur onal and glial apoptotic degeneration after experimental TBI in vivo.