Proteolysis Consistent with Activation of Caspase-7 after Severe Traumatic Brain Injury in Humans

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Abstract
The expression and proteolysis of caspase family proteins are involved in the initiation and execution of apoptosis, which has been reported to occur in human and experimental traumatic brain injury (TBI). Caspase-3, -6, and -7 belong to the group of executioner caspases, which are cleaved and activated at the late, irreversible stage of apoptosis. Our previous studies demonstrated roles for caspase-1, -3, and -8 in humans after severe TBI. Here we report expression of caspase-7 mRNA and protein in humans after TBI (n = 16) and control brain-bank tissue (n = 6). Semiquantitative reverse transcription polymerase chain reaction showed no differences between caspase-7 mRNA in TBI patients versus controls (73 ± 24 vs. 85 ± 56 relative optical density [ROD], respectively). In contrast, Western blot analysis showed increased pro-caspase-7 in TBI patients versus controls (214 ± 30 vs. 1 ± 1 ROD, respectively), as well as an increase in the ∼20 kD proteolytic fragment in TBI patients versus controls (86 ± 13 vs. 22 ± 12 ROD, respectively), consistent with activation of caspase-7 after TBI in humans. Immunohistochemical analysis showed that cells expressing caspase- 7 included astrocytes and neurons and possibly other glial cell types and infiltrated inflammatory cells. These data show that caspase-7 and its cleavage product are increased in human brain after TBI in many central nervous system, as well as noncentral nervous system, cell types. Thus, caspase-7 may play a role in the glial and inflammatory responses, and possibly neuronal death, after TBI in humans.