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This study tested the differences of meningitis and non-meningitis of Streptococcus suis (SS). In this study, an infected pig model of streptococcal meningitis was established. Compared with the non-meningitis Streptococcus suis group (JZLQ001 group), the meningitis Streptococcus suis group (JZLQ022) exhibited neurological symptoms, such as ataxia and foaming at the mouth, and the brain showed a large area of congestion at 5 days post-infection (p.i.). Moreover, bacterial counts, white blood cells (WBCs), neutrophils, and blood glucose in the blood reached a peak and were significantly higher than those of the JZLQ001 group at 3 days p.i. These values then decreased at 5 days p.i. However, the content of total protein in the blood was lower in the JZLQ022 group than that in the JZLQ001 group, and the difference was most significant at 5 days p.i. When neurological symptoms appeared on 5 days p.i., the bacterial counts in the brain in the JZLQ022 group were significantly higher than those in the JZLQ001 group. The levels of cytokines in the peripheral blood and cerebrospinal fluid (CSF) were an important indicator of inflammation. By ELISA detection, the secretion levels of IL-6, IL-8, and IL-17 in the peripheral blood in the JZLQ022 group were significantly higher than those in the JZLQ001 group at 12 and 24 h and 3 days p.i.; however, TNF-α showed no difference. At 5 days p.i., the secretion levels of IL-6, IL-8, and IL-17 in the JZLQ022 group were significantly lower than those in the JZLQ001 group. The results were similar in CSF. HE staining revealed that the JZLQ022 group exhibited neuronophagia and hyperemia in the brain, but no change was found in the JZLQ001 group. A further study investigating the impact of meningitis Streptococcus suis on blood-brain barrier (BBB) integrity found that the brain tissue content of endogenous IgG in the JZLQ022 group was significantly higher than that in the JZLQ001 group. The present study demonstrated that pigs infected with meningitis and non-meningitis Streptococcus suis exhibit significant differences in immunological aspects such as bacterial counts, WBCs, neutrophils, blood glucose and total protein in the peripheral blood, the secretion levels of IL-6, IL-8, and IL-17, and BBB integrity. These data provide the necessary evidence to better understand SS meningitis. [ABSTRACT FROM AUTHOR]