Control of Neuroinflammation through Radiation-Induced Microglial Changes

Abstract

Microglia, the innate immune cells of the central nervous system, play a pivotal role in the modulation of neuroinflammation. Neuroinflammation has been implicated in many diseases of the CNS, including Alzheimer's disease and Parkinson's disease. It is well documented that microglial activation, initiated by a variety of stressors, can trigger a potentially destructive neuroinflammatory response via the release of pro-inflammatory molecules, and reactive oxygen and nitrogen species. However, the potential anti-inflammatory and neuroprotective effects that microglia are also thought to exhibit have been under-investigated. The application of ionising radiation at different doses and dose schedules may reveal novel methods for the control of microglial response to stressors, potentially highlighting avenues for treatment of neuroinflammation associated CNS disorders, such as Alzheimer's disease and Parkinson's disease. There remains a need to characterise the response of microglia to radiation, particularly low dose ionising radiation.

Keywords: TSPO; antioxidants; cytokines; microglia; mitochondria; neuroinflammation.

Figure 1

Ionising radiation modulates inflammatory response in a healthy brain by altering microglial functional states. Low dose ionising radiation (left) may reduce the number of activated microglia, increasing antioxidants and anti-inflammatory cytokines and thus having a neuroprotective effect when compared to a control brain (middle). High dose ionising radiation (right) increases the number of activated microglia, which increases oxidants and pro-inflammatory cytokines, creating a neuroinflammatory state.

Figure 2

Low dose ionising radiation strengthens immunity in the healthy brain and reduces neurodegenerative disease by changing microglial functional states. A healthy brain exposed to low dose ionising radiation may experience anti-inflammatory effects, whereas in a degenerative brain, such as in Alzheimer’s disease, low dose ionising radiation may lessen the severity of neuroinflammation and promote a shift towards a more “normal” brain environment.