Traumatic brain injury

Summary

Traumatic brain injury (TBI) results from mechanical force to the brain and encompasses a spectrum from concussion to severe injury. Neuroinflammation following TBI is a major determinant of secondary injury and long-term outcome. Microglia are the primary innate immune responders to TBI and are activated within minutes of injury.

Microglial Relevance

Microglia are rapidly activated following TBI, shifting from homeostatic to damage-sensing states within hours. In the acute phase, microglial phagocytosis clears cellular debris through P2RY12, TREM2, and TAM receptor pathways. Chronic microglial activation following TBI contributes to secondary neurodegeneration. Repetitive mild TBI, as in contact sports, causes persistent microglial activation associated with CTE (chronic traumatic encephalopathy). C1Q-C3-mediated synaptic pruning contributes to cognitive decline post-TBI. P2RY12 and CX3CR1 expression are downregulated in activated post-TBI microglia.

Sources

Evidence State

human tissuesingle-cell RNA-seqanimal modelin vitro assay

Key Microglial Targets

Last reviewed: June 1, 2026