Related Experiment Video
Updated: Jul 28, 2025
Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice
Published on: May 4, 2015
USP14 inhibition promotes recovery by protecting BBB integrity and attenuating neuroinflammation in MCAO mice
Wenzhong Hou1, Jianping Yao2, Junjie Liu2
1Department of Cerebrovascular Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qianyuan, China.
Aim:
Blood-brain barrier (BBB) dysfunction is one of the hallmarks of ischemic stroke. USP14 has been reported to play a detrimental role in ischemic brain injury. However, the role of USP14 in BBB dysfunction after ischemic stroke is unclear.
Methods:
In this study, we tested the role of USP14 in disrupting BBB integrity after ischemic stroke. The USP14-specific inhibitor IU1 was injected into middle cerebral artery occlusion (MCAO) mice once a day. The Evans blue (EB) assay and IgG staining were used to assess BBB leakage 3 days after MCAO. FITC-detran test was slected to examine the BBB leakage in vitro. Behavior tests were conducted to evaluate recovery from ischemic stroke.
Results:
Middle cerebral artery occlusion increased endothelial cell USP14 expression in the brain. Furthermore, the EB assay and IgG staining showed that USP14 inhibition through IU1 injection protected against BBB leakage after MCAO. Analysis of protein expression revealed a reduction in the inflammatory response and chemokine release after IU1 treatment. In addition, IU1 treatment was found to rescue neuronal loss resulting from ischemic stroke. Behavior tests showed a positive effect of IU1 in attenuating brain injury and improving motor function recovery. In vitro study showed that IU1 treatment could alleviate endothelial cell leakage induced by OGD in cultured bend.3 cells through modulating ZO-1 expression.
Conclusions:
Our results demonstrate a role for USP14 in disrupting the integrity of the BBB and promoting neuroinflammation after MCAO.
Insights
USP14 inhibition protected the blood-brain barrier (BBB) after ischemic stroke. This treatment reduced neuroinflammation and improved motor function recovery in MCAO mice.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Blood-brain barrier (BBB) dysfunction is a key feature of ischemic stroke.
- USP14 is implicated in ischemic brain injury, but its role in BBB dysfunction remains unclear.
Purpose of the Study:
- To investigate the role of USP14 in disrupting BBB integrity following ischemic stroke.
- To evaluate the therapeutic potential of USP14 inhibition in a mouse model of ischemic stroke.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in mice.
- Administration of USP14-specific inhibitor IU1.
- Assessment of BBB leakage using Evans blue and IgG staining.
- In vitro assessment of endothelial cell permeability.
- Evaluation of neuroinflammation and neuronal loss.
- Behavioral tests for functional recovery.
Main Results:
- MCAO increased USP14 expression in brain endothelial cells.
- IU1 treatment significantly reduced BBB leakage and neuroinflammation.
- USP14 inhibition protected against neuronal loss and improved motor function recovery.
- In vitro studies confirmed IU1 alleviated endothelial cell leakage by modulating ZO-1.
Conclusions:
- USP14 plays a critical role in disrupting BBB integrity and promoting neuroinflammation after ischemic stroke.
- Inhibition of USP14 represents a potential therapeutic strategy for ischemic stroke by preserving BBB function.
More Related Videos
10:30Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice
Published on: October 20, 2016
09:08Induction of Ischemic Stroke and Ischemia-reperfusion in Mice Using the Middle Artery Occlusion Technique and Visualization of Infarct Area
Published on: February 2, 2017
