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NOD2 Expression in Streptococcus pneumoniae Meningitis and Its Influence on the Blood-Brain Barrier
Ying Wang1,2, Xinjie Liu1, Qi Liu2
1Department of Pediatrics, Qilu Hospital, Shandong University, 107# Wen Hua Xi Road, Jinan, Shandong 250012, China.
Abstract:
Streptococcus pneumoniae meningitis is one of the most common disorders seen in clinical practice. It is believed that the brain tissue immune injury is caused by the expression of pattern-recognition receptors (PRR) which can further induce the release of other cytokines and inflammatory cascades. The aim of this study is to investigate the expression of nucleotide-binding oligomerization domain 2 (NOD2) and inflammatory factors in rat brain tissues infected with Streptococcus pneumoniae and its influence on the blood-brain barrier (BBB) permeability. Rats were given an intracranial injection of Streptococcus pneumoniae to construct the Streptococcus pneumoniae meningitis rat models. The expression change curves of NOD2 and inflammatory factors at different time points (0 h, 12 h, 24 h, 48 h, and 7 d) after Streptococcus pneumoniae were evaluated by enzyme-linked immunosorbent assay (ELISA). Western blotting analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were engaged to examine the expression of NOD2. Furthermore, the changing processes of pathological characteristics, nervous system score, cerebral oedema, and BBB permeability were observed. Our results showed that NOD2 expression began to increase in the 12 h after Streptococcus pneumoniae infection group, while the remaining inflammatory factors were not obviously increased. Meanwhile, the levels of NOD2, as well as inflammatory factors IL-1β, TNF-α, and IL-6 were markedly elevated in 24 h and 48 h infection groups, which were consistent with the increases in BBB permeability and BWC, and the positive expression of NOD2 in the infected rat brain tissues was observed using immunohistochemistry (IHC). This study suggests that NOD2 might be related to the activation of inflammation pathways and the damage to the blood-brain barrier. NOD2 and inflammatory factors have played vital roles in the pathogenesis of Streptococcus pneumoniae meningitis.
Insights
Nucleotide-binding oligomerization domain 2 (NOD2) and inflammatory factors increase in Streptococcus pneumoniae meningitis, potentially damaging the blood-brain barrier (BBB). This research highlights NOD2's role in meningitis pathogenesis and BBB disruption.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Streptococcus pneumoniae meningitis is a common clinical disorder.
- Brain immune injury is linked to pattern-recognition receptor (PRR) expression, inducing inflammatory cascades.
- The role of NOD2 in pneumococcal meningitis and its effect on blood-brain barrier (BBB) integrity requires further investigation.
Purpose of the Study:
- To investigate the expression of nucleotide-binding oligomerization domain 2 (NOD2) and inflammatory factors in rat brain tissues during Streptococcus pneumoniae meningitis.
- To determine the influence of NOD2 and inflammatory factors on blood-brain barrier (BBB) permeability.
- To elucidate the role of NOD2 in the pathogenesis of Streptococcus pneumoniae meningitis.
Main Methods:
- Streptococcus pneumoniae meningitis rat models were established via intracranial injection.
- Expression levels of NOD2 and inflammatory factors (IL-1β, TNF-α, IL-6) were measured using ELISA, Western blotting, and qRT-PCR at various time points.
- Pathological characteristics, neurological scores, cerebral edema, and BBB permeability were assessed, with NOD2 expression visualized by immunohistochemistry (IHC).
Main Results:
- NOD2 expression increased significantly starting at 12 hours post-infection.
- Marked elevation of NOD2, IL-1β, TNF-α, and IL-6 levels occurred at 24 and 48 hours, correlating with increased BBB permeability.
- Positive NOD2 expression was confirmed in infected rat brain tissues via IHC.
Conclusions:
- NOD2 expression is upregulated during Streptococcus pneumoniae meningitis and may contribute to inflammation.
- NOD2 and associated inflammatory factors play a significant role in the pathogenesis of pneumococcal meningitis.
- The study suggests a link between NOD2 activation, inflammatory pathways, and blood-brain barrier damage in this condition.
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