Experimental Bacterial Meningitis in the Rabbit: Cerebrospinal Fluid Changes and Its Relation to Leukocyte Response

Lindquist, Lars; Lundbergh, P; Hedström, K.-G.; Hansson, Lars‐Olof; Hultman, E.

doi:10.3109/00365548709032409

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…Experimental meningitis model with PCW. A previously described meningitis model in female New Zealand White rabbits (3.5 to 4.5 kg) was used (10). Briefly, 0.25 ml of CSF was collected from the cisterna magna, after which an equal volume of the pneumococcal antigen suspension was injected.…”

Section: Methodsmentioning

confidence: 99%

Effects of Polysaccharide Fucoidin on Cerebrospinal Fluid Interleukin-1 and Tumor Necrosis Factor Alpha in Pneumococcal Meningitis in the Rabbit

et al. 1999

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The inflammatory response in bacterial meningitis is mediated by cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1), which are produced in the subarachnoid space by different cells, e.g., leukocytes, astrocytes, and microglia. The recruitment of leukocytes into the cerebrospinal fluid (CSF) has been shown to contribute to the neurological damage in this disease, a process which could be enhanced by treatment with antibiotics. In this study, we have used a rabbit meningitis model for two sets of experiments with intracisternal (i.c.) injections ofStreptococcus pneumoniae. First, pneumococcal cell wall (PCW) components were injected i.c., inducing an inflammatory response with pleocytosis and increased levels of CSF TNF-α) and IL-1 at 6 and 12 h after PCW injection. Treatment with fucoidin, known to inhibit leukocyte rolling, abolished pleocytosis and inhibited the release of TNF-α and IL-1. In the second experiment, live pneumococcal bacteria were injected i.c. and treatment with one dose of ampicillin (40 mg/kg of body weight intravenously) was given 16 h after induction of meningitis, causing a sevenfold increase in CSF leukocytes over a 4-h period. CSF IL-1 levels at 16 h were high but did not increase further at 20 h. Also, CSF TNF-α levels were high at 16 h and tended to increase at 20 h. Fucoidin treatment prevented the antibiotic-induced increase of CSF leukocytes but had no effect on the TNF-α and IL-1 levels. Taken together, fucoidin reduced CSF TNF-α and IL-1 levels in acute bacterial meningitis induced by PCW fragments but had no effect later in the course of the disease, when live bacteria were used and an inflammatory increase was caused by a dose of antibiotics.

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Section: Methodsmentioning

confidence: 99%

Effects of Polysaccharide Fucoidin on Cerebrospinal Fluid Interleukin-1 and Tumor Necrosis Factor Alpha in Pneumococcal Meningitis in the Rabbit

et al. 1999

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“…Experimental meningitis model. A previously described meningitis model in female New Zealand White rabbits (2.0 to 3.5 kg) was used (6). Briefly, 0.25 ml of CSF was collected from the cisterna magna, into which an equal volume of live bacteria was then injected.…”

Section: Methodsmentioning

confidence: 99%

The Polysaccharide Fucoidin Inhibits the Antibiotic-Induced Inflammatory Cascade in Experimental Pneumococcal Meningitis

Granert

Raud

Lindquist

1998

Clin Diagn Lab Immunol

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There is evidence that the treatment of bacterial meningitis with antibiotics liberates harmful bacterial products in the subarachnoid space (SAS). This enhances meningeal inflammation and in particular the recruitment of leukocytes into the cerebrospinal fluid (CSF), which has been shown to be more harmful than beneficial in this disease. In this study, we used a rabbit meningitis model based on intracisternal injection of live Streptococcus pneumoniae. Ampicillin (40 mg/kg of body weight given intravenously [i.v.] 16 h after induction of meningitis) caused a fivefold increase in CSF leukocytes over a 4-h period. Inhibition of leukocyte rolling by treatment with the polysaccharide fucoidin (10 mg/kg, i.v.) prevented the enhanced leukocyte extravasation into the SAS and attenuated the leakage of plasma proteins over the blood-brain barrier. These results suggest that certain polysaccharides that block leukocyte rolling have the potential to reduce leukocyte-dependent central nervous system damage in bacterial meningitis.

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“…Also, of no less importance is the fact that this rabbit model is a useful tool to analyze damage in the hippocampus due to meningitis (269). Similarly, Lindquist et al described the establishment of a rabbit model based on the use of a conventional head holder and on the percutaneous puncture by hand of the cisternae magnae of rabbits (148). Finally, Bhatt et al developed a model of meningogenic labyrinthitis via i.cist.…”

Section: Rat and Rabbit Modelsmentioning

confidence: 99%

Animal Models ofStreptococcus pneumoniaeDisease

2008

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SUMMARY Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.

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Experimental Bacterial Meningitis in the Rabbit: Cerebrospinal Fluid Changes and Its Relation to Leukocyte Response

Cited by 7 publications

References 19 publications

Effects of Polysaccharide Fucoidin on Cerebrospinal Fluid Interleukin-1 and Tumor Necrosis Factor Alpha in Pneumococcal Meningitis in the Rabbit

Effects of Polysaccharide Fucoidin on Cerebrospinal Fluid Interleukin-1 and Tumor Necrosis Factor Alpha in Pneumococcal Meningitis in the Rabbit

The Polysaccharide Fucoidin Inhibits the Antibiotic-Induced Inflammatory Cascade in Experimental Pneumococcal Meningitis

Animal Models ofStreptococcus pneumoniaeDisease

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