7-Nitroindazole, but not aminoguanidine, attenuates the acute inflammatory responses and brain injury during the early phase of Escherichia coli meningitis in the newborn piglet.
We evaluated the anti-inflammatory and neuroprotective effects of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole and aminoguanidine, which predominantly inhibits inducible nitric oxide synthase, 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. 7-Nitroindazole significantly attenuated the meningitis-induced acute inflammatory responses such as increased intracranial pressure, decreased cerebrospinal fluid (CSF) glucose concentration, and CSF leukocytosis at 2 h. However, meningitis-induced CSF leukocytosis at 4 h and increased CSF lactate and tumor necrosis factor alpha levels were not significantly attenuated. Reduced cerebral cortical cell membrane Na(+),K(+)-ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain cell membrane dysfunction, were also significantly improved with 7-nitroindazole treatment. In contrast, although aminoguanidine significantly attenuated the increase in the CSF tumor necrosis factor alpha level, it failed to attenuate the acute inflammation and the ensuing brain injury in bacterial meningitis. In summary, 7-nitroindazole, but not aminoguanidine, significantly attenuated the acute inflammatory responses and brain injury during the early phase of neonatal bacterial meningitis.
Park
W S
WS
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chang
Y S
YS
Lee
M
M
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D001927:Brain Diseases / Q000209:etiology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000737:chemistry / Q000201:enzymology; D002555:Cerebrospinal Fluid / Q000166:cytology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005947:Glucose / Q000032:analysis / Q000134:cerebrospinal fluid; D006146:Guanidines / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D007249:Inflammation / Q000517:prevention & control*; D019344:Lactic Acid / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D007964:Leukocytosis; D015227:Lipid Peroxidation; D020814:Meningitis, Escherichia coli / Q000134:cerebrospinal fluid / Q000150:complications* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D019001:Nitric Oxide Synthase; D005947:Glucose; C004479:pimagedine; C080122:7-nitroindazole