Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Leib, Stephen L.; Kim, Y S; Chow, Lucian; Sheldon, R. A.; Täuber, Martin G.

doi:10.1172/jci119084

Cited by 218 publications

(173 citation statements)

References 58 publications

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“…In bacterial meningitis Bcl-2 was expressed in apoptotic hippocampal neurons (9). Bacterial meningitis leads to oxidative stress, which has been shown to trigger neuronal necrosis and apoptosis in the central nervous system (4,9,25). Therefore, we also expected that neuronal damage would be increased in Bcl-2 knockout mice.…”

Section: Discussionmentioning

confidence: 99%

“…Survivors of meningitis often suffer from severe neurological sequelae (3,11). The pathological substrate for these long-term problems is neocortical and hippocampal neuronal damage, as observed at autopsy, by hippocampal magnetic resonance imaging volumetry, and in animal models (8,10,25,33,47,44). Neuronal apoptosis and necrosis are caused by direct toxicity of bacterial compounds and the inflammatory reaction of the host (6,21,38,40,43,47).…”

mentioning

confidence: 99%

“…Neuronal apoptosis and necrosis are caused by direct toxicity of bacterial compounds and the inflammatory reaction of the host (6,21,38,40,43,47). They are mediated by free radicals, excitatory amino acids, and caspases (4,5,22,25,26,34,43).…”

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confidence: 99%

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Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

Wellmer¹,

Mering²,

Spreer³

et al. 2004

Infect Immun

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Necrotic and apoptotic neuronal cell death can be found in pneumococcal meningitis. We investigated the role of Bcl-2 as an antiapoptotic gene product in pneumococcal meningitis using Bcl-2 knockout (Bcl-2 ؊/؊ ) mice. By using a model of pneumococcal meningitis induced by intracerebral infection, Bcl-2-deficient mice and control littermates were assessed by clinical score and a tight rope test at 0, 12, 24, 32, and 36 h after infection. Then mice were sacrificed, the bacterial titers in blood, spleen, and cerebellar homogenates were determined, and the brain and spleen were evaluated histologically. The Bcl-2-deficient mice developed more severe clinical illness, and there were significant differences in the clinical score at 24, 32, and 36 h and in the tight rope test at 12 and 32 h. The bacterial titers in the blood were greater in Bcl-2-deficient mice than in the controls (7.46 ؎ 1.93 log CFU/ml versus 5.16 ؎ 0.96 log CFU/ml [mean ؎ standard deviation]; P < 0.01). Neuronal damage was most prominent in the hippocampal formation, but there were no significant differences between groups. In situ tailing revealed only a few apoptotic neurons in the brain. In the spleen, however, there were significantly more apoptotic leukocytes in Bcl-2-deficient mice than in controls (5,148 ؎ 3,406 leukocytes/mm 2 versus 1,070 ؎ 395 leukocytes/mm 2 ; P < 0.005). Bcl-2 appears to counteract sepsis-induced apoptosis of splenic lymphocytes, thereby enhancing clearance of bacteria from the blood.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

Wellmer¹,

Mering²,

Spreer³

et al. 2004

Infect Immun

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“…Glutathione S-transferases (GST) are ubiquitous proteins whose primary function is related to detoxification of endo-and exogenous toxic molecules, thus protecting cells from oxidative stress (34,35). Previous studies demonstrated that GBS is capable of triggering oxidative burst in mammalian cells (11,36). The increase of the expression of GST in HUVECs under interaction with GBS might represent a protective mechanism displayed by endothelial cells to protect them against oxidative molecules generated or activated during such cell-bacterium interaction, but more experiments are necessary.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Group B Streptococcus induces tyrosine phosphorylation of annexin V and glutathione S-transferase in human umbilical vein endothelial cells

Santos

Penha²,

Mattos‐Guaraldi³

et al. 2009

Int J Mol Med

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Abstract. Group B Streptococcus (GBS), a human pathogen that causes infection and invasive diseases in newborns, pregnant women and immunocompromised adults, has been shown to invade human umbilical vein endothelial cells (HUVECs). The objective of this study was to investigate the molecular mechanisms underlying GBS-HUVEC interaction, focusing specifically on the responsiveness of host protein tyrosine kinase (PTK). We found that GBS serotypes III and V induced actin reorganization and formation of stress fibers into HUVECs. Since rearrangements of the actin cytoskeleton into eukaryotic cells are usually associated with the activation of PTK, we decided to follow the expression of this class of kinases in the course of the interaction. Unexpectedly, treatment of HUVECs with genistein greatly increased both cytoadherence and intracellular viability, for all GBS strains studied. GBS increased tyrosine phosphorylation of two proteins with an apparent molecular mass of 35 and 23 kDa in HUVECs as demonstrated by Western blot analysis with antiphosphotyrosine antibodies. Mass spectra analysis identified these proteins as annexin V and glutathione S-transferase. Studies are in progress to identify the role of these two proteins on GBS-HUVEC interaction.

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“…Several events involving cytokines, chemokines and oxidative stress have been observed during the inflammatory response contributing to brain dysfunction and this is mainly caused by the host immune response rather than by BM pathogen per se [12,13]. Genetic factors, such as single-nucleotide polymorphisms (SNPs) in DNA repair genes and in immune response genes have been shown to be associated with BM occurrence [11,14].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in DNA Repair Gene XRCC1 (Arg194Trp) and (Arg399Gln) and their Role in the susceptibility of Bacterial Meningitis

Pinheiro¹,

Fontes²,

Oliveira³

et al. 2015

J Meningitis

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Meningitis is a contagious infectious disease with high rates of mortality. Most pathogenic microbes in humans have the ability to cause bacterial meningitis. However, the most common pathogens are Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). It was found that the susceptibility to this infectious disease may be related to genetic characteristics of the host, such as the occurrence of single nucleotide polymorphisms (SNPs). In our previous work, association of SNPs in DNA repair genes with bacterial meningitis (BM) was demonstrated. In this study we evaluated two non-synonymous SNPs of the repair gene XRCC1 Arg194Trp (rs 1799782) and Arg399Gln (rs 25487) in patients with BM and health volunteers. The patient genotypes were investigated by PCR-RFLP. DNA damages were quantified using the genomic DNA with formamidopyrimidine DNA-glycosylase (FPG). Cytokines and chemokines were quantified from cerebrospinal fluid samples from BM patients. Concerning the SNP XRCC1 Arg194Trp, none association was found relation to BM. However, a higher frequency of heterozygous genotype for XRCC1 Arg399Gln was observed in the control group compared to the BM group (P = 0.043; OR = 0.426). DNA damage and cytokine/chemokines levels were not positively correlated with polymorphic genotypes. In conclusion, there is an indication that the SNP XRCC1 Arg399Gln could have a possible protective effect against BM.

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Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci.

Cited by 218 publications

References 58 publications

Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

Group B Streptococcus induces tyrosine phosphorylation of annexin V and glutathione S-transferase in human umbilical vein endothelial cells

Polymorphisms in DNA Repair Gene XRCC1 (Arg194Trp) and (Arg399Gln) and their Role in the susceptibility of Bacterial Meningitis

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