1,721,139 research outputs found
Experimental meningitis by Streptococcus pneumoniae and Neisseria meningitidis in rodents
No full textBacterial meningitis (BM) is a global public health issue that affects patients of all ages. The two leading causes of BM worldwide are Streptococcus pneumoniae (the pneumococcus) and Neisseria meningitidis (the meningococcus). Despite the use of antibiotics and vaccines, both pneumococcal meningitis (PM) and meningococcal meningitis (MM) result in high case fatality rates and long-term neurological sequelae. Moreover, increasing resistance to first-line antibiotics, limited vaccine coverage, serotype replacement in vaccinated population, and lack of adjunctive therapies to control brain damage are all matters of concern in the management of PM and MM.
The availability of animal models of PM and MM is crucial to characterize the pathogenetic and pathophysiologic mechanisms of disease as well as to identify novel antimicrobial agents, adjuvant therapies and vaccine candidates. Historically, animal models of BM employed large animals to mimic the disease in humans, such as monkeys for MM and rabbits for PM. However, since the introduction of rodents, both rats and mice have demonstrated to be robust, reliable, and suitable species for modeling both PM and MM. Depending on the route of infection, the dose of bacterial inoculum, the animal age and strain, different experimental readouts are obtained that permit to answer specific scientific questions.
This chapter describes the main features of two models of PM and MM developed in the infant rat and adult mouse, respectively. Each model system presents unique characteristics that allow to study different aspects of the disease.
The broad range of different forms of brain injury that can be observed in the PM infant rat model enables to study the entire spectrum of the pathophysiology of brain damage in PM and allows to evaluate novel therapeutic strategies and their impact on long-term neurological sequelae. The MM mouse model is suitable to investigate the role of meningococcal virulence factors in the disease, the host–parasite interactions in the central nervous system, and the efficacy of drugs to control the infection and limit brain damage in MM
[In search of strategies for preventing brain damage as a sequela of bacterial meningitis]
No full textMultiplication of bacteria within the central nervous system compartment triggers a host response with an overshooting inflammatory reaction which leads to brain parenchyma damage. Some of the inflammatory and neurotoxic mediators involved in the processes leading to neuronal injury during bacterial meningitis have been identified in recent years. As a result, the therapeutic approach to the disease has widened from eradication of the bacterial pathogen with antibiotics to attenuation of the detrimental effects of host defences. Corticosteroids represent an example of the adjuvant therapeutic strategies aimed at downmodulating excessive inflammation in the infected central nervous system. Pathophysiological concepts derived from an experimental rat model of bacterial meningitis revealed possible therapeutic strategies for prevention of brain damage. The insights gained led to the evaluation of new therapeutic modalities such as anticytokine agents, matrix metalloproteinase inhibitors, antioxidants, and antagonists of endothelin and glutamate. Bacterial meningitis is still associated with persistent neurological sequelae in approximately one third of surviving patients. Future research in the model will evaluate whether the neuroprotective agents identified so far have the potential to attenuate learning disabilities as a long-term consequence of bacterial meningitis
[Meningitis (II)--acute bacterial meningitis]
No full textAcute meningitis is a medical emergency, particularly in patients with rapidly progressing disease, mental status changes or neurological deficits. The majority of cases of bacterial meningitis are caused by a limited number of species, i.e. Streptococcus pneumoniae, Neisseria meningitis, Listeria monocytogenes, group B Streptococci (Streptococcus agalactiae), Haemophilus influenzae and Enterobacteriaceae. Many other pathogens can occasionally cause bacterial meningitis, often under special clinical circumstances. Treatment of meningitis includes two main goals: Eradication of the infecting organism, and management of CNS and systemic complications. Empiric therapy should be initiated without delay, as the prognosis of the disease depends on the time when therapy is started. One or two blood cultures should be obtained before administering the first antibiotic. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. It is safer to choose regimens with broad coverage, as they can usually be modified within 24-48 hours, when antibiotic sensitivities of the infecting organism become available. Adjunctive therapy with dexamethasone is also administered in severely ill patients concomitantly with the first antibiotic dose. In patients who are clinically stable and are unlikely to be adversely affected if antibiotics are not administered immediately, including those with suspected viral or chronic meningitis, a lumbar puncture represents the first step, unless there is clinical suspicion of an intracerebral mass lesion. Findings in the CSF and on CT scan, if performed, will guide the further diagnostic work-up and therapy in all patients
[What is your diagnosis? Basal meningitis and rhombencephalitis. Blood culture positive for Listeria monocytogenes].
No full textAn in vitro model of central nervous system infection and regeneration: neuronal stem cells as targets of brain damage and regenerative therapies in bacterial meningitis.
No full textIn bacterial meningitis cortical brain damage is associated with changes in parenchymal MMP-9/TIMP-1 ratio and increased collagen type IV degradation
No full textAdverse outcome in bacterial meningitis is associated with the breakdown of the blood-brain barrier (BBB). Matrix-metalloproteinases (MMPs) facilitate this process by degradation of components of the BBB. This in turn results in acute complications of bacterial meningitis including edema formation, increased intracranial pressure and subsequent ischemia. We determined the parenchymal balance of MMP-9 and TIMP-1 (tissue inhibitor of MMP) and the structural integrity of the BBB in relation to cortical damage in an infant rat model of pneumococcal meningitis. The data demonstrate that the extent of cortical damage is significantly associated with parenchymal gelatinolytic activity and collagen type IV degradation. The increased gelatinolysis was found to be associated with a brain parenchymal imbalance of MMP-9/TIMP-1. These findings provide support to the concept that MMPs mediated disruption of the BBB contributes to the pathogenesis of bacterial meningitis and that protection of the vascular unit may have neuroprotective potential
Meningokokkeninfektion: Zwei Fälle zur Breite des klinischen Spektrums
No full textInvasive meningococcal infections show a broad clinical picture including sepsis and meningitis. Here we report on a case of sepsis and a case of meningitis, two clinical manifestations of meningococcal infections with striking differences in the clinical presentation and outcome. Meningococcal sepsis is characterized by a systemic release of endotoxins, that triggers an intense cytokine response of the host that can lead to shock and multi organ failure and death within hours. Meningococcal meningitis occurs when bacteria breach into the subarachnoidal and ventricular space during bacteremia and mortality is much lower that in sepsis. Thus meningitis may be seen as a consequence of lower pathogenicity and/or more efficient host control of the meningococci compared to sepsis
Strategies to prevent neuronal damage in paediatric bacterial meningitis
Full text linkPURPOSE OF REVIEW: The mortality of bacterial meningitis can reach 30%, and up to 50% of survivors suffer from persisting neurological deficits as a consequence of the disease. The incidence of neurological sequelae of bacterial meningitis has not improved over the last decade. Adjunctive therapeutic options are limited, and ongoing research into the pathophysiology of brain damage in bacterial meningitis aims at providing the scientific basis for future development of more efficient adjunctive options. RECENT FINDINGS: In a population with good access to health care, dexamethasone given before or at the time of initiation of antibiotic therapy acts beneficially in paediatric pneumococcal meningitis, but not in meningococcal meningitis. In experimental animal models, brain-derived neurotrophic factor protected against brain injury and improved hearing while melatonin, which has antioxidant properties among other effects, reduced neuronal death. Transgene technology can be used to provide new insights into the pathophysiology of the disease and to identify potential therapeutic targets. SUMMARY: Although dexamethasone improves outcome of bacterial meningitis under defined circumstances, the morbidity of bacterial meningitis still remains unacceptably high. Experimental models may help to identify new therapeutic strategies to further improve the neurological outcome in young children suffering from bacterial meningitis
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