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Updated: Jul 13, 2026

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
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.
Background:
Neuroinflammation drives the secondary damage following traumatic brain injury (TBI), a process largely regulated by the balance between pro-inflammatory and anti-inflammatory microglial phenotypes. Microglial activation requires rapid cytoskeletal remodeling to organize signaling complexes, yet the role of the actin-bundling protein Fascin1 in this process remains unexplored. This study investigates whether Fascin1 acts as a key upstream regulator of microglial polarization and neuroinflammatory signaling during the early stages of TBI.
Methods:
We established neuroinflammation models using controlled cortical impact (CCI) in mice and LPS-stimulated BV2 cells. Fascin1 was silenced via intracerebroventricular siRNA injection in vivo and transfection in vitro. We evaluated the effects on inflammation, neuronal survival, and key signaling pathways via qRT-PCR, Western blotting, immunofluorescence, ELISA, and behavioral assessments.
Results:
Fascin1 expression was significantly upregulated in both the injured cortex of TBI mice and LPS-activated microglia. Knockdown of Fascin1 effectively inhibited the pro-inflammatory state while enhancing the anti-inflammatory state, reducing cytokine secretion and attenuating neuronal apoptosis. In vivo, Fascin1 silencing significantly alleviated neurological deficits and reduced tissue loss. Mechanistically, Fascin1 depletion was associated with a concurrent dampening of the phosphorylation of critical inflammatory mediators, specifically AKT, mTOR, STAT3, and NF-κB p65.
Conclusions:
Our findings demonstrate that Fascin1 promotes neuroinflammation during acute TBI. Fascin1 appears to modulate the activity of the AKT/mTOR, STAT3, and NF-κB signaling cascades, thereby shifting microglia toward a pro-inflammatory state.
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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