Recombinant TsP53 mitigates inflammation and blood-brain barrier disruption in CLP-induced septic mice

Sepsis-associated encephalopathy (SAE), a neurological complication of sepsis without direct CNS infection, currently lacks established pharmacological therapy. Key pathological features include excessive microglial activation and blood-brain barrier (BBB) disruption. Our prior work showed that recombinant Trichinella spiralis 53-kDa glycoprotein (rTsP53) modulates intestinal endothelial tight junctions in septic mice by downregulating inflammation.

We analyzed inflammatory factor levels and performed bioinformatics analysis on cerebrospinal fluid (CSF) from SAE patients. In a cecal ligation and puncture (CLP)-induced septic mouse model, we assessed brain inflammatory cytokines, BBB permeability, tight junction protein expression, microglial activation, and transcription factor p65 levels. Mice were prophylactically treated with rTsP53 prior to septic insult.

CSF from SAE patients showed significantly elevated inflammatory factors and upregulated leukocyte migration/chemotaxis pathways. CLP-induced septic mice exhibited increased brain inflammatory cytokines, enhanced BBB permeability, reduced tight junction protein expression, microglial activation, and elevated p65. Prophylactic rTsP53 treatment decreased pro-inflammatory cytokines (IL-6, IL-17A) and p65, increased anti-inflammatory factors (IL-4, IL-13), and alleviated BBB damage.

Prophylactic rTsP53 mitigates sepsis-induced brain inflammation and BBB disruption in mice by modulating the microglial response. These findings provide preclinical evidence supporting the further exploration of rTsP53 as a potential preventive agent for SAE.