Every year, around 3 to 5 million people in the EU and the US suffer a traumatic brain injury (TBI). In most cases, it is a mild brain injury (mTBI) due to a closed head injury (CHI) caused by falls, traffic accidents, contact sports, or violence. Although the symptoms of mTBI may resolve within days or weeks, up to 20 percent of those affected suffer from persistent physical, cognitive, and behavioral impairments, leading to a reduced quality of life and an increased risk of neuropsychiatric disorders, including mood disorders and dementia.
Central role of ASC in maintaining neuroinflammation
Our immune cells contain small emergency systems called inflammasomes. When an alarm is triggered, the protein ASC helps activate this emergency button by forming aggregates, which produce inflammatory substances. Inflammasomes are crucial for chronic neuroinflammation, and secondary damage after trauma, but their role in mild traumatic brain injury is largely unknown. "In our study, we focused primarily on inflammasome activation and its functional significance in CHI models," says corresponding and co-first author Dr. Sergio Castro-Gomez, neurology physician-scientist at the Center for Neurology and junior research group leader at the Institute of Physiology II at UKB. He is a member of the Cluster of Excellence ImmunoSensation3 and the Transdisciplinary Research Area (TRA) "Present Pasts" at the University of Bonn.
In mouse models without ASC, the researchers were able to show that the activation of microglia, the immune cells in the central nervous system, and the star-shaped support cells in brain tissue, known as astrocytes, was weaker. In addition, fewer inflammatory substances such as interleukin-1β were produced. The mice also showed fewer memory impairments in tests. On the other hand, ASC aggregates spread rapidly and exacerbated the damage. "Our results show that the inflammasome adapter protein ASC is a key element in neuroinflammatory reactions and cognitive impairment after mild brain injury," says co-first author Dr. Tao Li.
ASC blockers could stop inflammation and promote healing
Further research is needed to gain a comprehensive understanding of the specific temporal involvement of inflammasomes in different degrees of injury severity and risk factors for neurodegeneration. Castro-Gomez sums up: "However, based on our current findings, pharmacological interventions targeting ASC could help mitigate neuroinflammation and possibly promote neuroprotection, thereby improving recovery after injury and preventing further neurodegeneration and impairment."