3-Aminobenzamide, a poly (ADP-ribose) synthetase inhibitor, attenuates theacute inflammatory responses and brain injury in experimental Escherichia coli meningitis in the newborn piglet

The aim of the present study was to evaluate the anti-inflammatory and neur oprotective effects of a poly (ADP-ribose) synthetase inhibitor 3-aminobenz amide during the early phase of experimental bacterial meningitis in the ne wborn piglet Meningitis was induced by intracisternal injection of 10(8) co lony forming units of Escherichia coil in 100 mul of saline. 3-Aminobenzami de, given 30 mg kg(-1) as a bolus i.v, injection 30 min before induction of meningitis, significantly attenuated the meningitis-induced acute inflamma tory responses such as increased cerebrospinal fluid (CSF) lactate concentr ation, CSF leukocytosis and increased CSF tumor necrosis factor-alpha level . However, meningitis-induced increase in intracranial pressure and decreas e in CSF glucose level were not significantly improved. Increased cerebral cortical cell membrane lipid peroxidation products (conjugated dienes) and decreased brain ATP/phosphocreatine levels observed in the meningitis group were also significantly improved with 3-aminobenzamide treatment However, the improvement of reduced Na+,K+-ATPase activity did not reach a statistic al significance (p = 0.06). In summary, 3-aminobenzamide significantly atte nuated the acute inflammatory responses and the ensuing brain injury during the early phase of neonatal bacterial meningitis. These findings suggest t hat poly (ADP-ribose) synthetase inhibitors such as 3-aminobenzamide might be a promising novel anti-inflammatory and neuroprotective adjuvant therapy in neonatal bacterial meningitis.