Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1142 23

The present study assessed the role of PARP [poly(adenosine diphosphate-ribose) polymerase] activation in experimental pneumococcal meningitis. Mice with a targeted disruption of the PARP 1 gene were protected against meningitis-associated central nervous system complications including blood-brain barrier breaching and increase in intracranial pressure. This beneficial effect was paralleled by a significant reduction in meningeal inflammation, as evidenced by significantly lower cerebrospinal fluid leukocyte counts and interleukin-1beta, -6, and tumor necrosis factor-alpha concentrations in the brain (compared with infected wild-type mice). The reduction in inflammation and central nervous system complications was associated with an improved clinical status of infected, PARP 1-deficient mice. A similar protective effect was achieved by PARP inhibition using 3-aminobenzamide, the pharmacologic efficacy of which was confirmed by a marked attenuation of meningitis-induced poly(ADP)ribose formation. When the rat brain-derived endothelial cell line GP8.3 was cocultured with macrophages, exposure to pneumococci induced endothelial cell death and was paralleled by PARP activation and a reduction in the oxidized form of cellular nicotinamide adenine dinucleotide content. Treatment with 3-aminobenzamide significantly attenuated cellular nicotinamide adenine dinucleotide depletion and pneumococci-induced cytotoxicity. Thus, PARP activation seems to play a crucial role in the development of meningitis-associated central nervous system complications and pneumococci-induced endothelial injury. Inhibitors of PARP activation could provide a potential therapy of acute bacterial meningitis.
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PMID:Meningitis-associated central nervous system complications are mediated by the activation of poly(ADP-ribose) polymerase. 1180 92