3-Aminobenzamide, a poly (ADP-ribose) synthetase inhibitor, attenuates the acute 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 neuroprotective effects of a poly (ADP-ribose) synthetase inhibitor 3-aminobenzamide during the early phase of experimental bacterial meningitis in the newborn piglet. Meningitis was induced by intracisternal injection of 10(8) colony forming units of Escherichia coli in 100 microl of saline. 3-Aminobenzamide, given 30 mg kg(-1) as a bolus i.v. injection 30 min before induction of meningitis, significantly attenuated the meningitis-induced acute inflammatory responses such as increased cerebrospinal fluid (CSF) lactate concentration, CSF leukocytosis and increased CSF tumor necrosis factor-alpha level. However, meningitis-induced increase in intracranial pressure and decrease 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 statistical significance (p = 0.06). In summary, 3-aminobenzamide significantly attenuated the acute inflammatory responses and the ensuing brain injury during the early phase of neonatal bacterial meningitis. These findings suggest that poly (ADP-ribose) synthetase inhibitors such as 3-aminobenzamide might be a promising novel anti-inflammatory and neuroprotective adjuvant therapy in neonatal bacterial meningitis.
Park
W S
WS
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. wspark@smc.samsung.co.kr
Chang
Y S
YS
Lee
M
M
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D001549:Benzamides / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism; D015169:Colony Count, Microbial; D004660:Encephalitis / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli / Q000302:isolation & purification; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D007958:Leukocyte Count; D020814:Meningitis, Escherichia coli / Q000097:blood / Q000134:cerebrospinal fluid / Q000382:microbiology / Q000473:pathology*; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D011064:Poly Adenosine Diphosphate Ribose; D019344:Lactic Acid; C025160:3-aminobenzamide; D005947:Glucose