KACTThe meningeal inflammatory response to a heat-killed mutant unencapsulated strain of type I11 group B Streptococcus (GBS) was studied in a newborn piglet model. GBS (10" colonyforming unit equivalents) or saline (control) was inoculated intraventricularly. Serial cerebrospinal fluid measurements were done at baseline and over the course of the next 24 h for cytochemical changes and production of tumor necrosis factor (TNF) and prostaglandins. In separate experiments, we defined the time course of early changes during the first 6 h and dose response relationship over a range of inocula lo6 to 10" colonyforming unit equivalents. The intraventricular inoculation of the heat-killed unencapsulated GBS induced marked leukocytosis and increased protein by 6 h. These changes were preceded by a several hundredfold increase in TNF (maximum at 2 h) and prostaglandins (maximum at 2-4 h). The early and sharp rise in TNF suggests its pivotal role in initiating the inflammatory cascade. The magnitude of the inflammatory response increased with increasing bacterial dose over the range studied. To study the effect of encapsulation of GBS in the induction of meningeal inflammation, we compared the response to the unencapsulated mutant strain with that to the encapsulated parent strain. The encapsulated strain produced much smaller inflammatory changes, and only with high doses of bacteria. The GBS cell wall appeared to be the primary bacterial product triggering inflammation. Intraventricular injection of the heat-killed unencapsulated GBS with exposed cell wall can serve as a valid model for studying neonatal meningitis. ( Neonatal meningitis continues to be associated with high mortality and morbidity despite effective antibiotic therapy and advanced intensive care technology. The current incidence is 0.4-1.011 000 live births (1, 2), and current mortality is 20-40% with long-term neurologic sequelae in as many as onethird of the survivors (3). Over the past few years, studies on meningitis in human and in animal models have increased our understanding of the pathogenesis of infection and pathophysiology. It has been shown that bacterial products initiate a chain of inflammatory reactions with the formation of inflammatory cytokines and biochemical mediators (4-7). These events result in injury to the vascular lining of the brain and alteration in the CSF dynamics, brain metabolism, and the control of cerebral blood flow. Most animal models of bacterial meningitis use adult animals. It is important to develop a neonatal animal model to study the pathophysiologic consequences of meningeal inflammation on the immature brain. It is the objective of this study to develop an animal model of neonatal meningitis using a common neonatal pathogen. GBS is a common causative organism of neonatal sepsis and GBS type 111, in particular, is a common cause of neonatal meningitis (8).In Gram-positive organisms, the techoic acid-containing cell wall has been suggested to be responsible for the initiation of inflammation. In an adult rabbit ...

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