Related Experiment Video
Updated: Sep 9, 2026
The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse
Published on: July 25, 2011
TRIM45 causes neuronal damage by aggravating microglia-mediated neuroinflammation upon cerebral ischemia and
Qian Xia1, Gaofeng Zhan1, Meng Mao2
1Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
Abstract:
Excessive and unresolved neuroinflammation is a key component of the pathological cascade in brain injuries such as ischemic stroke. Tripartite motif-containing 45 (TRIM45) is a ubiquitin E3 ligase involved in various critical biological processes. However, the role of TRIM45 in cerebral ischemia remains unknown. Here, we found that the TRIM45 protein was highly expressed in the peri-infarct areas of mice subjected to cerebral ischemia and reperfusion injury induced by middle cerebral artery occlusion. This study systemically evaluated the putative role of TRIM45 in the regulation of neuroinflammation during ischemic injury and the potential underlying mechanisms. We found that TRIM45 knockdown significantly decreased proinflammatory cytokine and chemokine production in primary cultured microglia challenged with oxygen-glucose deprivation and reoxygenation (OGD/R) treatment. Mechanistically, we demonstrated that TRIM45 constitutively interacted with TAB2 and consequently facilitated the Lys-63-linked polyubiquitination of TAB2, leading to the formation of the TAB1-TAK1-TAB2 complex and activation of TAK1, which was ultimately followed by activation of the nuclear factor-kappa B (NF-κB) signaling pathway. In an in vitro coculture Transwell system, downregulation of TRIM45 expression also inhibited the OGD/R-induced activation of microglia and alleviated neuronal apoptosis. More importantly, microglia-specific knockdown of TRIM45 in mice significantly reduced the infarct size, mitigated neurological deficit scores, and improved cognitive function after ischemic stroke. Taken together, our study reveals that the TRIM45-TAB2 axis is a crucial checkpoint that controls NF-κB signaling in microglia during cerebral ischemia and reperfusion injury. Therefore, targeting TRIM45 may be an attractive therapeutic strategy.
Insights
Tripartite motif-containing 45 (TRIM45) regulates neuroinflammation after ischemic stroke by activating the NF-κB pathway in microglia. Targeting TRIM45 may offer a new therapeutic approach for brain injuries.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Neuroinflammation is a critical factor in brain injury, particularly ischemic stroke.
- The role of Tripartite motif-containing 45 (TRIM45), a ubiquitin E3 ligase, in cerebral ischemia is not understood.
Purpose of the Study:
- To investigate the function and mechanism of TRIM45 in regulating neuroinflammation during ischemic stroke.
- To evaluate TRIM45 as a potential therapeutic target for ischemic brain injury.
Main Methods:
- Assessed TRIM45 expression in a mouse model of cerebral ischemia and reperfusion.
- Utilized primary microglia cultures and oxygen-glucose deprivation/reoxygenation (OGD/R) models.
- Investigated TRIM45 interaction with TAB2 and its role in the NF-κB signaling pathway.
- Employed microglia-specific TRIM45 knockdown in vivo.
Main Results:
- TRIM45 expression was elevated in peri-infarct areas following ischemic stroke.
- TRIM45 knockdown reduced pro-inflammatory cytokine production in microglia exposed to OGD/R.
- TRIM45 facilitates NF-κB activation via the TRIM45-TAB2-TAK1 complex.
- Microglia-specific TRIM45 reduction decreased infarct size and improved neurological function in mice.
Conclusions:
- The TRIM45-TAB2 axis is a key regulator of microglial NF-κB signaling in cerebral ischemia-reperfusion injury.
- TRIM45 plays a significant role in exacerbating neuroinflammation and brain damage post-stroke.
- Targeting TRIM45 presents a promising therapeutic strategy for treating ischemic stroke.
