Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat

The activation of poly(ADP-ribose) polymerase, a DNA base excision repair e nzyme, is indicative of DNA damage. This enzyme also undergoes site-specifi c proteolysis during apoptosis. Because both DNA fragmentation and apoptosi s are known to occur following experimental brain injury, we investigated t he effect of lateral fluid percussion brain injury on poly(ADP-ribose) poly merase activity and cleavage. Male Sprague-Dawley rats (n = 52) were anesth etized, subjected to fluid percussion brain injury of moderate severity (2. 5-2.8 atm), and killed at 30 min, 2 h, 6 h, 24 h, 3 days, or 7 days postinj ury. Genomic DNA from injured cortex at 24 h, but not at 30 min, was both f ragmented and able to stimulate exogenous poly(ADP-ribose) polymerase. Endo genous poly(ADP-ribose) polymerase activity, however, was enhanced in the i njured cortex at 30 min but subsequently returned to baseline levels. Sligh t fragmentation of poly(ADP-ribose) polymerase was detected in the injured cortex in the first 3 days following injury, but significant cleavage was d etected at 7 days postinjury. Taken together, these data suggest that poly( ADP-ribose) polymerase-mediated DNA repair is initiated in the acute posttr aumatic period but that subsequent poly(ADP-ribose) polymerase activation d oes not occur, possibly owing to delayed apoptosis-associated proteolysis, which may impair the repair of damaged DNA.