Tumour Necrosis Factor-α Inhibition Improves Stroke Outcome in a Mouse Model of Rheumatoid Arthritis

Area of Science:

• Neuroscience
• Immunology
• Cardiovascular Medicine

Background:

• Rheumatoid arthritis (RA) is linked to increased cardiovascular risk, including myocardial infarction.
• The impact of RA on stroke incidence and outcomes remains unclear, necessitating further investigation.

Purpose of the Study:

• To investigate the effects of RA on Ischemia/Reperfusion (I/R) brain injury in a mouse model.
• To assess the therapeutic potential of Infliximab, a tumor necrosis factor-α (TNF-α) inhibitor, in mitigating stroke-related damage in RA.

Main Methods:

• Utilized a TNF-α-dependent mouse model of RA, treating animals with vehicle or Infliximab prior to inducing I/R brain injury.
• Analyzed stroke size, neurological performance, blood-brain barrier (BBB) integrity, immune cell infiltration, tight junction protein (TJP) levels, matrix metalloproteinase (MMP) expression, and lipid peroxidation.

Main Results:

• RA mice exhibited larger strokes, poorer neurological function, increased BBB disruption, decreased TJPs (claudin-5, occludin), elevated MMP-3 and -9, and enhanced lipid peroxidation.
• Infliximab treatment reversed these pathological changes, restoring the RA mice's phenotype to baseline levels.
• Increased microglia and macrophage infiltration correlated with BBB degradation and stroke severity.

Conclusions:

• RA exacerbates stroke outcomes by compromising blood-brain barrier integrity through reduced TJPs and increased MMPs and oxidative stress.
• Infliximab effectively ameliorates stroke-related brain injury in a mouse model of RA.
• Targeting TNF-α with Infliximab presents a promising therapeutic strategy for reducing stroke burden in RA patients.