Astrocyte Reactivity Following Blast Induced Traumatic Brain Injury


Sophia Norman
Matthew Robson


By Sophia Norman, Neuroscience

Advisor: Matthew Robson


Traumatic brain injury (TBI) affects nearly 2.8 million people in the United States annually, contributing significantly to financial burden, disability, and death. Currently, there is a lack of any FDA approved treatment to alleviate the negative symptoms following TBI. Post injury, an inflammatory response occurs in the central nervous system contributing to the activation of astrocytes and microglia, a process referred to as gliosis. This inflammatory cascade is largely contributed by pro-inflammatory signaling molecules including interleukin-1α (IL-1α) and interleukin-1β (IL-1β). The interleukin-1 receptor associated kinase (IRAK4) is an essential component to the IL-1 signaling pathway and therefore may serve as a potential target to block this signaling. We hypothesize that IRAK4 may be a viable target to block the interleukin-1- mediated changes in astrocytes including the formation of neurotoxic astrocytes seen in neurodegenerative diseases. Blast-induced TBI resulted in an increase in IL-1α, IL-1β, and the glial fibrillary acidic protein (GFAP) expression in mice, indicating the presence of reactive astrocytes. Astrocytes treated with IL-1α in culture showed an increase in gfap mRNA expression, as well as increased serping1 expression, a characteristic gene of proinflammatory astrocytes. Pre-treatment with an IRAK4 inhibitor (AS2444697), blocked IL-1 induced increases in gfap and serping1 expression. Inhibiting IRAK4 demonstrated efficacy in mitigating astrogliosis and the formation of neurotoxic astrocytes, highlighting its potential as a viable therapeutic target for neurodegenerative disorders.



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