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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the use of antibiotics, the prognosis of bacterial meningitis is still poor due to central nervous system (CNS) complications, such as brain edema formation, cerebrovascular alterations, and intracranial hemorrhage. Experimental studies with animal models have given new insights into its pathophysiology during the acute phase of the disease. In recent years, genetically engineered mice have become a powerful tool in investigating the role of particular genes by targeted deletion and have also been applied in bacterial meningitis research. By using knockout mice, new knowledge of the roles of the different cytokines, proteases, and oxidants involved in the inflammatory cascade has emerged. In the future, temporal and cell type-specific control of gene expression will provide even more information on the impact of a particular gene on meningitis-induced brain damage.
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PMID:Using knockout mice to study experimental meningitis. 1462 31

The astroglial water channel aquaporin-4 (AQP4) facilitates water movement into and out of brain parenchyma. To investigate the role of AQP4 in meningitis-induced brain edema, Streptococcus pneumoniae was injected into cerebrospinal fluid (CSF) in wild type and AQP4 null mice. AQP4-deficient mice had remarkably lower intracranial pressure (9 +/- 1 versus 25 +/- 5 cm H2O) and brain water accumulation (2 +/- 1 versus 9 +/- 1 microl) at 30 h, and improved survival (80 versus 0% survival) at 60 h, through comparable CSF bacterial and white cell counts. Meningitis produced marked astrocyte foot process swelling in wild type but not AQP4 null mice, and slowed diffusion of an inert macromolecule in brain extracellular space. AQP4 protein was strongly up-regulated in meningitis, resulting in a approximately 5-fold higher water permeability (P(f)) across the blood-brain barrier compared with non-infected wild type mice. Mathematical modeling using measured P(f) and CSF dynamics accurately simulated the elevated lower intracranial pressure and brain water produced by meningitis and predicted a beneficial effect of prevention of AQP4 upregulation. Our findings provide a novel molecular mechanism for the pathogenesis of brain edema in acute bacterial meningitis, and suggest that inhibition of AQP4 function or up-regulation may dramatically improve clinical outcome.
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PMID:Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis. 1569 11

To determine the contribution of vascular endothelial growth factor (VEGF) to cerebral edema formation in bacterial meningitis, we used a VEGF neutralizing antibody to block VEGF in rabbits, following induction of meningitis by intracisternal inoculation with 10(9) heat-killed pneumococci. At 8 h, cerebrospinal fluid (CSF) VEGF was significantly elevated in infected untreated animals, and correlated with CSF white blood cell (WBC) count (r=0.56, P=0.004), and brain water content (r=0.42, P=0.04). Blocking of VEGF did not attenuate brain edema, blood-brain barrier disruption, or CSF pleocytosis. The functional role of VEGF in the pathophysiology of BM remains elusive.
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PMID:Antibody neutralization of vascular endothelial growth factor (VEGF) fails to attenuate vascular permeability and brain edema in experimental pneumococcal meningitis. 1571 Apr 70

Bacterial meningitis is a medical emergency and is optimally managed in an intensive care environment. Despite the use of antibiotics, the prognosis of this disease is poor because of central nervous system complications such as brain edema formation, cerebrovascular alterations, intracranial hemorrhage, and hydrocephalus. Effective adjunctive therapies are still missing. Experimental studies with animal models have provided new insights into the pathophysiology during the acute phase of bacterial meningitis. In recent years, knockout mice have become a powerful tool to investigate the role of particular genes and have also been applied in bacterial meningitis research. The use of these mice offered new insights into the role of different cytokines, proteases, and oxidants involved in the inflammatory cascade. Translating this knowledge into new therapies will provide new treatment strategies for this serious disease in the future.
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PMID:Development of adjunctive therapies for bacterial meningitis and lessons from knockout mice. 1615 83

Increased vascular permeability causing vasogenic brain edema is characteristic for many acute neurological diseases such as stroke, brain trauma, and meningitis. Src family kinases, especially c-Src, play an important role in regulating blood-brain barrier permeability in response to VEGF, but also mediate leukocyte function and cytokine signalling. Here we demonstrate that pharmacological inhibition of Src or c-Src deficiency does not influence cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial outgrowth during experimental pneumococcal meningitis despite the increased cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL-2 and G-CSF as determined by protein array analysis. In contrast, inhibition of Src significantly reduced brain edema formation, lesion volume, and clinical worsening in cold-induced brain injury without decreasing cytokine/chemokine expression. While brain trauma was associated with increased cerebral VEGF formation, VEGF levels significantly declined during pneumococcal meningitis. Therefore, we conclude that in brain trauma blood-brain barrier tightness is regulated by the VEGF/Src pathway whereas c-Src does not influence brain edema formation and leukocyte function during bacterial meningitis.
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PMID:Differential regulation of blood-brain barrier permeability in brain trauma and pneumococcal meningitis-role of Src kinases. 1701 Mar 40

The balancing act between microbes and their host in commensal and disease states needs to be deciphered in order to fully treat and combat infectious diseases. The elucidation of microbial genome dynamics in each instance is therefore required. In this context, the major bacterial meningitis pathogens are Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae. In prokaryotic CNS pathogenesis both the intact organism as well as its released components can elicit disease, often resulting in neurological sequelae, neurodegeneration or fatal outcome. The study of microbial virulence in CNS disease is expected to generate findings that yield new information on the general mechanisms of brain edema and excitatory neuronal disturbances due to meningitis, with significant potential for discoveries that can directly influence and inspire new strategies for prevention and treatment of this serious disease.
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PMID:Microbial genome dynamics in CNS pathogenesis. 1736 50

Accumulating evidences have demonstrated that matrix metalloproteinases (MMPs) contribute to the pathophysiology of bacterial meningitis. MMPs facilitate leukocyte extravasation and brain edema by degradation of extracellular matrix components. Dexamethasone as adjunctive therapy to antibiotics has shown to have beneficial effects on pathophysiological changes and neurological outcome in children with meningitis and in animal models. However, the role of dexamethasone in the pathophysiology of pneumococcal meningitis is still unknown. The effects of antibiotics on MMPs in bacterial meningitis have not been evaluated so far. We have therefore intended to investigate the induction and expression of MMPs with special emphasis on the regulation of MMPs by dexamethasone and antibiotics in therapy of pneumococcal meningitis. In the present study, the expression of MMP-9 and MMP-2 mRNA in the brain of rats and the activity of MMP-9 and MMP-2 in the CSF of rats have been determined during the course of experimental bacterial meningitis and after treatment with an antibiotic plus dexamethasone. In the brain tissue of rats with Streptococcus pneumococcal meningitis, MMP-9 mRNA was obviously up-regulated after inoculation for 24 h (p<0.01) and then declined but was still greater than that in the brains of control rats after inoculation for 4 days (p<0.05) while the expression of MMP-2 remained at basal level. The expression of MMP-9 in the brains of rats inoculated with Streptococcus pneumoniae and treated by antibiotic was dose-dependent, up-regulated (p<0.01) but down-regulated after treatment with an antibiotic plus dexamethasone (p<0.01). However, the expression of MMP-9 mRNA did not change in the rats inoculated with sterile saline and treated with an antibiotic. The zymographic activity of MMP-9 and MMP-2 showed similar changes. The results indicated that the expression of MMP-9 mRNA and its activity might be increased after antibiotic treatment and inhibited after treatment with antibiotics plus dexamethasone; dexamethasone might have a beneficial effect on bacterial meningitis via down-regulation of the expression of MMP-9.
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PMID:Dexamethasone regulation of matrix metalloproteinase expression in experimental pneumococcal meningitis. 1837 3

Bacterial meningitis remains a major cause of death and neurological and hearing sequels. In adults, the death rate ranges from 16 to 37% in meningitis due to Pneumococcus pneumoniae and neurological sequels occur in 30 to 52% of survivors. In childhood, the prognosis is better, with a death rate ranging from 2 to 15%, higher for Pneumococcus pneumoniae. Seventy-five percent of children survive without any sequel, 15% with hearing disorders (up to 30% with Pneumococcus), and rarely (3-4%) present with mental retardation, motor deficit, or epilepsy. In addition to the type of germ, the risk of sequels is six times higher in case of Pneumococcus, several factors of poor prognosis are described on admission: degree of coma, neurological deficit, cranial nerve palsy, high protein level, high erythrocytes count and low leukocytes count in CSF (less than 600 or 1000 leukocytes per microliter). Any neurological complication such as epilepsy, stroke, brain edema, hydrocephalus, or hemodynamic failure will be correlated to a poor outcome. Hearing must be tested within 15 days, followed by audiologic consultation and MRI focused on labyrinths to detect early onset cochlear ossification. One year after meningitis, behavior and cognitive skills must be assessed, including IQ, memory, attention and executive functions, adaptive abilities, to set up specific educative and teaching strategies.
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PMID:[Long-term follow-up of bacterial meningitis - sequels in children and adults: incidence, type, and assessment issues]. 1939 75

We report a 4-year-old boy with fulminating meningitis caused by Haemophilus influenzae (Hib). He suddenly developed fever, vomiting and then somnolence. As bacterial meningitis was suspected, treatment with antibiotics was started at 12 hours after the onset. However, there was a rapid progression of severe brain edema and brain hernia, leading to clinical brain death. His clinical course and neuroradiological findings mimicked those in patients with acute encephalopathy, with cytokine profiles in cerebrospinal fluid demonstrating a marked increase of inflammatory cytokines. From a review of the literature, fulminating Hib meningitis may be classified into two disease types: DIC plus multiple organ failure and acute brain swelling types. The present case belongs to the latter type, in which cytokine storm seems to play an important pathogenic role.
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PMID:[Fulminating meningitis caused by Haemophilus influenzae with rapid progression of severe brain edema similar to acute encephalopathy]. 1992 44

We report a 57-year old female patient with a rapid and dramatic dynamic of whole brain edema caused by tuberculous meningitis. After initiation of tuberculostatic medication, general condition of the patient worsened and finally she was intubated due to a progredient loss of consciousness and respiratory insufficiency. Repeated cerebral computer tomography (CCT) revealed a global brain edema with slit ventricles and a dramatic progress of generalized brain swelling. Highly interesting, a rapid expanded regime of brain pressure monitoring and treatment according to a neurosurgical intensive standard ICP/CPP management protocol, which was complemented by the tuberculostatic therapy and high dose steroid application, dramatically improved the general conditions, so that the patient is now in a general condition which corresponds that before the occurrence of tuberculous meningitis. Thus, it is mandatory in situations with a rapid progressive brain swelling caused by bacterial meningitis to consider an intensified cerebral monitoring and stratified treatment protocol in order to avoid the devasting effects of a long lasting increase in intracranical pressure.
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PMID:Invasive pressure monitoring saves from tuberculous meningitis with fulminant generalized brain edema. 2211 Apr 66


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