The role of platelets, and effect of aspirin, on neuroinflammation in TB meningitis

Tuberculosis affecting the brain, called TB meningitis (TBM), is a lethal disease. Brain damage associated with TBM results from our own immune cells working in overdrive. Better understanding of this immune activation will help develop treatment to improve outcomes for patients. There is evidence that aspirin (an anti-clotting drug) improves outcome in TBM patients.

It is thought that aspirin reduces inflammation, but how it does this is not elucidated.

I will gather and analyze data from two clinical trials investigating the use of adding aspirin to standard treatment in TBM patients in South Africa, where rates of TBM are high. I will measure markers of inflammation in blood and spinal fluid before and during treatment.

I will take patient blood cells and add them to a lab model of the blood brain barrier (an important line of defense in preventing disease) and examine how these cells affect barrier function. This will demonstrate how immune cells behave in TBM patients and the effect of aspirin. I will correlate immune responses with patient outcome i.e. whether patients get better or suffer disability.

Improved understanding of mechanisms of brain inflammation has the potential to lead to development of new treatments for TBM patients.