Impact Induces Phagocytic Defect in Reactive Microglia

Area of Science:

• Neuroscience
• Biotechnology
• Cell Biology

Background:

• Traumatic brain injury (TBI) poses significant challenges in understanding neuroinflammation and neurodegeneration.
• In vitro models are crucial for studying cellular responses to TBI.
• Lipid metabolism is implicated in brain trauma and neurodegenerative diseases.

Purpose of the Study:

• To develop and utilize a TBI-on-a-chip model to investigate molecular and cellular changes post-impact.
• To assess the impact of TBI on microglial phagocytosis and neuronal function.
• To analyze alterations in the cellular lipidome following TBI.

Main Methods:

• Development of a TBI-on-a-chip model using primary microglia and neuronal networks.
• Utilized a pH-responsive amyloid β (AβpH) assay to measure microglial phagocytosis.
• Electrophysiological recordings to assess neuronal firing frequency.
• Lipidomic analysis of secreted lipids from impacted cells.

Main Results:

• Microglial phagocytosis was significantly reduced at 7 days post-impact in the TBI chip model.
• Neurons exhibited increased amyloid β uptake and decreased firing frequency at 7 days post-impact.
• Significant alterations were observed in lipid species from sphingomyelin, glycerophospholipid, and phosphatidylserine classes.

Conclusions:

• The TBI-on-a-chip model effectively recapitulates key cellular and molecular changes following brain injury.
• Impaired microglial function and neuronal activity, coupled with altered lipid metabolism, are critical consequences of TBI.
• These findings highlight the role of lipid metabolism in neuroinflammation resolution and neurodegeneration pathogenesis after TBI.