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Updated: Sep 3, 2025
A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury
Published on: June 20, 2017
Knockout of Sirt2 alleviates traumatic brain injury in mice
Wei Wang1, Qiu-Yuan Gong1, Lin Cai1
1Department of Neurosurgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Sirtuin 2 (SIRT2) inhibition or Sirt2 knockout in animal models protects against the development of neurodegenerative diseases and cerebral ischemia. However, the role of SIRT2 in traumatic brain injury (TBI) remains unclear. In this study, we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema, attenuated disruption of the blood-brain barrier, decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, reduced the activity of the effector caspase-1, reduced neuroinflammation and neuronal pyroptosis, and improved neurological function. Knockout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis. Our findings suggest that knockout of Sirt2 is neuroprotective against TBI; therefore, Sirt2 could be a novel target for TBI treatment.
Insights
Sirtuin 2 (SIRT2) knockout protects the brain after traumatic brain injury (TBI) by reducing inflammation and improving neurological function. This suggests SIRT2 is a potential therapeutic target for TBI treatment.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Sirtuin 2 (SIRT2) is implicated in neuroprotection in models of neurodegenerative diseases and cerebral ischemia.
- The specific role of SIRT2 in traumatic brain injury (TBI) has not been previously elucidated.
Purpose of the Study:
- To investigate the role of Sirtuin 2 (SIRT2) in a mouse model of traumatic brain injury (TBI).
- To determine if SIRT2 inhibition or knockout offers neuroprotection against TBI.
Main Methods:
- Utilized a mouse model of TBI and an in vitro mechanical stretch injury cell model.
- Assessed brain edema, blood-brain barrier integrity, NLRP3 inflammasome expression, caspase-1 activity, neuroinflammation, neuronal pyroptosis, and neurological function.
- Compared outcomes between wild-type and Sirt2 knockout mice.
Main Results:
- Sirt2 knockout significantly reduced brain edema and blood-brain barrier disruption in TBI mice.
- Knockout of Sirt2 attenuated NLRP3 inflammasome activation, caspase-1 activity, neuroinflammation, and neuronal pyroptosis.
- Improved neurological function was observed in Sirt2 knockout mice following TBI.
- In vitro studies confirmed that Sirt2 knockout decreased NLRP3 inflammasome and pyroptosis.
Conclusions:
- Sirtuin 2 (SIRT2) knockout demonstrates significant neuroprotective effects against traumatic brain injury (TBI).
- Targeting SIRT2 may represent a novel therapeutic strategy for mitigating TBI-induced damage and improving outcomes.
