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

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.
 ...
PMID:Meningitis-associated central nervous system complications are mediated by the activation of poly(ADP-ribose) polymerase. 1180 92

The loss of soluble brain antioxidants and protective effects of radical scavengers implicate reactive oxygen species in cortical neuronal injury caused by bacterial meningitis. However, the lack of significant oxidative damage in cortex [J. Neuropathol. Exp. Neurol. 61 (2002) 605-613] suggests that cortical neuronal injury may not be due to excessive parenchymal oxidant production. To see whether this tissue region exhibits a prooxidant state in bacterial meningitis, we examined the state of the major cortical antioxidant defenses in infant rats infected with Streptococcus pneumoniae. Adenine nucleotides were co-determined to assess possible changes in energy metabolism. Arguing against heightened parenchymal oxidant production, the high NADPH/NADP(+) ratio ( approximately 3:1) and activities of the major antioxidant defense and pentose phosphate pathway enzymes remained unchanged at the time of fulminant meningitis. In contrast, cortical ATP, ADP and total adenine nucleotides were on average decreased by approximately 25%. However, energy depletion did not lead to a significant decrease in adenylate energy charge (AEC). ATP depletion was likely a consequence of metabolic degradation, since it correlated with both the loss of total adenine nucleotides and accumulation of purine degradation products. Furthermore, the loss of ATP and decrease in AEC correlated significantly with the extent of neuronal injury. These results strongly suggest that energy depletion rather than parenchymal oxidative damage is involved in the observed cortical neuronal injury.
 ...
PMID:Impaired cortical energy metabolism but not major antioxidant defenses in experimental bacterial meningitis. 1276 48

The meningitis is a disease with high mortality rates capable to cause neurologic sequelae. The adenosine (the final product of ATP hydrolysis by ectonucleotidases), have a recognized neuroprotective actions in the central nervous system (CNS) in pathological conditions. The aim of the present study was evaluate the adenine nucleotides hydrolysis for to verify one possible role of ATP, ADP and AMP hydrolysis in inflammatory process such as meningitis. The hydrolysis was verified in cerebrospinal fluid (CSF) from human patients with aseptic and bacterial meningitis. Our results showed that the ATP hydrolysis was reduced 12.28% (P < 0.05) in bacterial meningitis and 22% (P < 0.05) in aseptic meningitis. ADP and AMP hydrolysis increased 79.13% (P < 0.05) and 26.37% (P < 0.05) in bacterial meningitis, respectively, and 57.39% (P < 0.05) and 42.64% (P < 0.05) in aseptic meningitis, respectively. This may be an important protective mechanism in order to increase adenosine production.
 ...
PMID:Adenine nucleotide hydrolysis in patients with aseptic and bacterial meningitis. 1871 98