DNA FRAGMENTATION AND NUCLEAR ENDONUCLEASE ACTIVITY IN RAT-BRAIN AFTER SEVERE CLOSED-HEAD INJURY

Previous studies have suggested that brain cells undergo apoptotic cel l death during several neurodegenerative disorders such as Alzheimer's disease, Parkinsonism and ischemic stroke. In the present study, apop totic DNA fragmentation and activation of nuclear endonuclease were ev aluated in rat brain cells after head trauma. Severe closed head injur y was induced in rats by the impact of a 450-g weight dropped from a h eight of 2 m. A 12% mortality was experienced after head trauma. Brain cell nuclei and DNA were isolated at intervals of 3, 10, 24 h, 3 and 10 days after head trauma. DNA fragmentation was measured by the rando m oligonucleotide-primed synthesis (ROPS) assay and was significantly increased with the maximum level of DNA fragmentation occurring at 10 h after trauma. The DNA and nuclei yields decreased 10 h after injury and remained at a reduced level at all subsequent sampling intervals. The DNA fragmentation induced after severe head trauma was accompanied by an increase in the activity of the Ca/Mg-dependent endonuclease as sociated with apoptosis. These data indicate that severe head injury i s associated with significant brain cell death by apoptosis.