Fascin1 exacerbates neuroinflammation and neuronal injury in acute TBI by orchestrating the AKT/mTOR, STAT3, and

Wei You1, Yiting Wu1, Yiru Fang1

  • 1Department of Neurosurgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, Fujian 363119, China.

Abstract

Insights

Fascin1 promotes neuroinflammation after traumatic brain injury (TBI) by activating pro-inflammatory microglial responses. Silencing Fascin1 reduces inflammation, protects neurons, and improves outcomes in TBI models.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Neuroinflammation exacerbates secondary damage in traumatic brain injury (TBI).
  • Microglial polarization between pro-inflammatory and anti-inflammatory states is critical in TBI.
  • The role of the actin-bundling protein Fascin1 in microglial activation and TBI is unknown.

Purpose of the Study:

  • To investigate Fascin1 as a regulator of microglial polarization in TBI.
  • To determine Fascin1's role in neuroinflammatory signaling during acute TBI.

Main Methods:

  • Established TBI models using controlled cortical impact (CCI) in mice and LPS-stimulated BV2 cells.
  • Silenced Fascin1 using siRNA in vivo and in vitro.
  • Assessed inflammation, neuronal survival, and signaling pathways via molecular and behavioral methods.

Main Results:

  • Fascin1 expression increased in TBI cortex and LPS-activated microglia.
  • Fascin1 knockdown shifted microglia to an anti-inflammatory phenotype, reducing cytokines and neuronal apoptosis.
  • Fascin1 silencing in vivo improved neurological function and reduced tissue damage.
  • Fascin1 depletion decreased phosphorylation of AKT, mTOR, STAT3, and NF-κB.

Conclusions:

  • Fascin1 promotes neuroinflammation in acute TBI.
  • Fascin1 modulates AKT/mTOR, STAT3, and NF-κB signaling to drive pro-inflammatory microglial states.

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