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Updated: Dec 17, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Up-regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury
Pengzhan Zhao1, Chong Li1, Binglin Chen1
1Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Microglial cells are key component of central nervous system (CNS) and mediate the immune response of the brain under physiological or pathological conditions. It tends to activate into a pro-inflammatory M1 phenotype after traumatic brain injury (TBI) and promote secondary brain damage. Recently, necroptosis was found to promote microglial activation and neuroinflammation after TBI. However, the mechanism and specific interventions of microglial necroptosis after TBI remain poorly investigated. Here, we reported that overexpress the charged multivesicular body protein 4b (CHMP4B) which is a core member of the endosomal sorting required for transport complex III (ESCRT-III) significantly decreased the level of necroptosis in microglia, improved neurological function recovery and protected against cell death after TBI. Further investigation showed that forkhead transcription factor O1 (FOXO1) was a crucial transcription factor that increased CHMP4B transcription by binding to the promoter region, thereby inhibiting necroptosis in microglia. Collectively, our findings demonstrated that CHMP4B relieved microglial necroptosis and neuroinflammation after TBI, and promote the recovery of nerve function. FOXO1 is an important factor in promoting CHMP4B expression. This study provides the novel viewpoint for TBI prevention and treatment.
Insights
Overexpressing charged multivesicular body protein 4b (CHMP4B) reduces microglial necroptosis and neuroinflammation after traumatic brain injury (TBI). This enhances neurological recovery and highlights FOXO1
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are central to brain immune responses, but their pro-inflammatory activation post-traumatic brain injury (TBI) exacerbates damage.
- Necroptosis has emerged as a contributor to microglial activation and neuroinflammation following TBI.
- The precise mechanisms and therapeutic targets for microglial necroptosis in TBI remain largely unexplored.
Purpose of the Study:
- To investigate the role of charged multivesicular body protein 4b (CHMP4B) in microglial necroptosis after TBI.
- To explore the therapeutic potential of modulating CHMP4B for TBI treatment.
- To elucidate the regulatory pathway involving FOXO1 and CHMP4B in microglial necroptosis.
Main Methods:
- Overexpression of CHMP4B in microglia.
- Assessment of necroptosis levels in microglia.
- Evaluation of neurological function and cell death after TBI.
- Analysis of FOXO1 binding to the CHMP4B promoter region.
Main Results:
- Overexpression of CHMP4B significantly reduced microglial necroptosis.
- CHMP4B overexpression improved neurological function recovery and protected against cell death post-TBI.
- FOXO1 was identified as a key transcription factor that enhances CHMP4B transcription by binding to its promoter, thereby inhibiting necroptosis.
Conclusions:
- CHMP4B alleviates microglial necroptosis and neuroinflammation following TBI, promoting nerve function recovery.
- FOXO1 plays a critical role in upregulating CHMP4B expression, offering a novel therapeutic target.
- This study provides a new perspective for the prevention and treatment of TBI.
