Neural-Cardiac Inflammasome Axis after Traumatic Brain Injury.
Robert W KeaneRoey HadadXavier O ScottErika D L R M Cabrera RanaldiJon Pérez-BárcenaJuan Pablo de Rivero VaccariPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Traumatic brain injury (TBI) affects not only the brain but also peripheral organs like the heart and the lungs, which influences long-term outcomes. A heightened systemic inflammatory response is often induced after TBI, but the underlying pathomechanisms that contribute to co-morbidities remain poorly understood. Here, we investigated whether extracellular vehicles (EVs) containing inflammasome proteins are released after severe controlled cortical impact (CCI) in C57BL/6 mice and cause activation of inflammasomes in the heart that result in tissue damage. The atrium of injured mice at 3 days after TBI showed a significant increase in the levels of the inflammasome proteins AIM2, ASC, caspases-1, -8 and -11, whereas IL-1β was increased in the ventricles. Additionally, the injured cortex showed a significant increase in IL-1β, ASC, caspases-1, -8 and -11 and pyrin at 3 days after injury when compared to the sham. Serum-derived extracellular vesicles (EVs) from injured patients were characterized with nanoparticle tracking analysis and Ella Simple Plex and showed elevated levels of the inflammasome proteins caspase-1, ASC and IL-18. Mass spectrometry of serum-derived EVs from mice after TBI revealed a variety of complement- and cardiovascular-related signaling proteins. Moreover, adoptive transfer of serum-derived EVs from TBI patients resulted in inflammasome activation in cardiac cells in culture. Thus, TBI elicits inflammasome activation, primarily in the atrium, that is mediated, in part, by EVs that contain inflammasome- and complement-related signaling proteins that are released into serum and contribute to peripheral organ systemic inflammation, which increases inflammasome activation in the heart.
Keyphrases
- traumatic brain injury
- end stage renal disease
- severe traumatic brain injury
- inflammatory response
- mass spectrometry
- ejection fraction
- newly diagnosed
- chronic kidney disease
- mild traumatic brain injury
- induced apoptosis
- peritoneal dialysis
- prognostic factors
- clinical trial
- skeletal muscle
- stem cells
- cell death
- pulmonary artery
- high fat diet induced
- nlrp inflammasome
- resting state
- vena cava
- toll like receptor
- early onset
- functional connectivity
- metabolic syndrome
- double blind
- drug induced
- endoplasmic reticulum stress
- patient reported outcomes
- blood brain barrier
- high performance liquid chromatography
- cell proliferation
- spinal cord
- atomic force microscopy
- left atrial appendage
- capillary electrophoresis