Role of Ang/tie2 Axis Imbalance Between Pericytes and Endothelial Cells In The Pathogenesis of Pneumococcal Meningitis

Objective: Even with early diagnosis and proper treatment, the mortality and the disability rates of patients with pneumococcal meningitis remain high, and there is an urgent need to develop new treatment strategies. Methods: This study is based on an in vitro co-culture cell model of pneumococcal meningitis (co-culture of pericytes and cerebral microvascular endothelial cells), and employs strategies such as antisense RNA interference technology, transcellular electrical impedance assay, Pull Down, luciferase reporter gene system, immunofluorescence multilabeling, and laser scanning confocal microscopy. Results: Pneumolysin stimulates the excessive release of Ang2, leading to an imbalance in the Ang/Tie2 signalling axis between pericytes and endothelial paracellular secretion; pericyte apoptosis mediated by the PI3K/Akt pathway, disruption of endothelial tight junctions, and the opening of the BBB promote cascade amplification of inflammatory responses, which may be an effective mechanism for the lethality and disability of the disease Conclusions: The potential of Ang/Tie2 signalling axis-targeting agents as an adjunctive therapeutic target for this disease, with strong translational practical clinical implications