School of Medicine

Brain inflammation may be the reason behind muscle fatigue after infection and injury

Neuroinflammation is a result of your central nervous system’s immune response. (Image: nopparit/E+ via Getty Images)

Infectious or chronic diseases such as long COVID, Alzheimer’s disease and traumatic brain injury can cause inflammation in the brain, or neuroinflammation, that weakens muscles. While scientists are aware of this link between inflammation and muscle weakness, the molecules and processes involved have been unclear.

In our research, our team of neuroscientists and biologists uncovered the hidden conversation between the brain and muscles that triggers muscle fatigue, and potential ways to treat it.

Neuroinflammation and muscle fatigue

Neuroinflammation results when your central nervous system – the brain and spine – activates its own immune system to protect itself against infection, toxins, neurodegeneration and traumatic injury. Neuroinflammatory reactions primarily occur in the brain. But for unknown reasons, patients also experience many symptoms outside the central nervous system, such as debilitating fatigue and muscle pain.

To solve this puzzle, we studied brain inflammation in the context of three different diseases: bacterial infection in E. coli-induced meningitis; viral infection in COVID-19; and neurodegeneration in Alzheimer’s disease. Then, we analyzed how these immune changes affect muscle performance.

We measured immune changes in the brains of fruit flies and mice infected with live bacteria, viral proteins or neurotoxic proteins. After the initial accumulation of toxic molecules in the brain that commonly increase in response to stresses such as infection, the brain produces high levels of cytokines – chemicals that activate the immune system – that are released into the body. When these cytokines travel to muscles, they activate a series of chemical reactions that disrupts the ability of the powerhouse of cells – mitochondria – to produce energy.

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