The neuroprotective effect of cerebral poly(ADP-ribose) polymerase inhibition in a rat model of global ischemia

In the present study, the effect of poly(ADP-ribose) polymerase (PARP) inhi bition on rat cortical energy state was investigated at 24 h after global c erebral ischemia induced by permanent bilateral common carotid artery ligat ion plus transient hypotension. The specific PARP inhibitor 3-aminobenzamid e was injected 10 min before induction of ischemia at a dosage of 5, 10, an d 20 mg/kg intracerebroventricularly. Twenty-four hours after ischemia cort ical PARP enzyme activity increased from 0.425 +/- 0.144 to 0.794 +/- 0.193 units/mg protein. Cerebral ischemia was associated by a decrease in adenos ine triphosphate (ATP) and phosphocreatine concentrations to 72.5 and 76.8% of controls, respectively. In addition, an 1.9- and 2.2-fold increase in a denosine monophosphate and adenosine was observed. Specific PARP inhibition with 10 mg/kg 8-aminobenzamide protected the rat energy state by preservin g cortical phosphocreatine and NAD(+). Cortical AIP was not changed signifi cantly after PARP inhibition. In conclusion, activation of the nuclear enzy me PARP plays an important role in cerebral energy metabolism during rat gl obal ischemia. Therefore, specific PARP inhibition may offer new strategies in the therapy of vascular diseases such as stroke. (C) 2000 Elsevier Scie nce ireland Ltd. All rights reserved.