Site-specific cleavage of 28S rRNA as a marker of traumatic brain injury.

Abstract

A cleavage product of 28S rRNA was isolated from ipsilateral hippocampus of rat brain subjected to lateral fluid percussion induced traumatic brain injury (TBI). Northern blot analysis demonstrated that the corresponding cDNA fragment hybridized to 28S rRNA and three cleavage products. Two of the cleaved rRNA fragments (1.3 kb and 0.9 kb) were also observed in differentiated PC12 cells undergoing apoptosis induced by NGF withdrawal. The third fragment (0.6 kb) was detected only in rat brain tissue subjected to trauma, suggesting specific cleavage of 28S following TBI. The 0.6-kb fragment was found only in cortex and hippocampus ipsilateral to the trauma site, but not in brain stem, contralateral cortex or contralateral hippocampus. 28S rRNA cleavage was detected beginning 2 h after trauma and reflected injury severity. Although cleavage of 28S rRNA has been reported in association with apoptosis in white blood cells and apoptosis occurs in the experimental head injury model used, the pattern of 28S rRNA cleavage observed with TBI differs from those observed in apoptotic PC12 cells or those reported for white blood cells. Thus, whereas 28S rRNA fragmentation appears to be a marker of posttraumatic brain injury, its precise role in the secondary injury process remains to be established.