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Pathophysiology of experimental pneumococcal meningitis induced by
peripheral inoculation
NSC 88-2314-B-006-045
87 8 1 88 7 31
E-mail: liucc@mail.ncku.edu.tw
Pathophysiology of experimental pneumococcal meningitis induced by
peripheral inoculation
NSC 88-2314-B-006-045
87 8 1 88 7 31
!"!#$%!&
E-mail: liucc@mail.ncku.edu.tw
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Abstract
Bacterial meningitis (BM) remains a common, life-threatening disease despite recent major advances in antimicrobial therapy and rapid diagnostic techniques. The most common causative agents were Haemophilus
influenzae type b (Hib), group B β-hemolytic streptococci, Streptococcus pneumoniae, Escherichia coli, and Neisseria meningitidis. In the United States, approximately 15,000 cases of BM occur annually, with a mortality rate of 10% in infants, and about 15% of surviors have persistent neurologic sequelae. In Taiwan, BM continues to cause significant mortality and morbidity, Hib is the most common pathogen in childhood bacterial meningitis, followed by S. pneumoniae. Usually, bacterial meningitis is preceded with the colonization and penetration of nasopharyngeal mucosal membranes by bacteria, followed by survival of bacteria in blood and transportation via circulation, and invasion of central nervous system. Thus, bacteremia frequently precedes or occurs concomitantly with BM. Tumor necrosis
factor-α (TNF-α) released by
monocytes/macrophages in response to bacterial endotoxin (LPS), has been implicated as a principal mediator in septic shock. Other cytokines such as IL-1 and IL-6 also synergizes with TNF-α in producing lethal shock or meningococcal meningitis'
Using a peripheral tracer with β-galactosidase activity, a simple method to quantify the degree of increased permeability of BBB during the development of bacterial meningitis was set up. Intracerebral injection of S. pneumoniae only induced one-stage-alteration of BBB and it was mediated by infiltrating neutrophils. Peripheral (i.v. or intraperitoneal) administration of S. pneumoniae could induce the maximal increase of BBB permeabilty at 3 h and 12 h after injection, respectively. The timing is coincident with their kinetics of the circulating TNFα production in sepsis. We have been successfully inducing S. pneumoniae meningitis through two stage intraperitoneal inoculation of the bacteria. In the second year study, we will further elucidate the role of TNFα in the pathogenesis of bacterial meningitis.
Keywords: bacterial meningitis, animal model, Streptococcus pneumoniae, cerebrospinal fluid,
TNFα.
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