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Updated: Dec 27, 2025
Autologous Blood Injection to Model Spontaneous Intracerebral Hemorrhage in Mice
Published on: August 24, 2011
MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in
Xiaodong Wu1,2, Jinting Wu3, Wenjie Hu4
1Key Laboratory of Noncoding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.
Background:
The aim of this study was to explore the role of hesperadin in intracerebral hemorrhage (ICH) mice, with the involvement of the mammalian ste20-like kinase 4 (MST4)/AKT signaling pathway.
Methods:
All mice were divided into four groups: sham group, sham+hesperidin group, ICH group, and ICH+hesperadin group. The effects of hesperadin were assessed on the basis of brain edema and neurobehavioral function. Furthermore, we observed MST4, AKT, phosphorylation of AKT (pAKT), and microtubule-associated protein light chain 3 (LC3) by western blotting. Protein localization of MST4 and LC3 was determined by immunofluorescence.
Results:
The expression of MST4 was upregulated at 12 h and 24 h after ICH. Brain edema was significantly decreased and neurological function was improved in the hesperadin treatment group compared to the ICH group (P < 0.05). Hesperadin decreases the expressions of MST and increases pAKT after ICH. Autophagy significantly increased in the ICH group, while hesperadin reduced this increase.
Conclusion:
Hesperadin provides neuroprotection against ICH by inhibiting the MST4/AKT signaling pathway.
Insights
Hesperadin protects the brain after intracerebral hemorrhage (ICH) by regulating the mammalian ste20-like kinase 4 (MST4)/AKT pathway, reducing brain edema and improving neurological function in mice.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Intracerebral hemorrhage (ICH) is a severe neurological condition.
- The mammalian ste20-like kinase 4 (MST4)/AKT signaling pathway's role in ICH is not fully understood.
- Hesperadin is a potential therapeutic agent for neurological disorders.
Purpose of the Study:
- To investigate the neuroprotective effects of hesperadin in a mouse model of ICH.
- To elucidate the involvement of the MST4/AKT signaling pathway in hesperadin's action.
- To assess the impact of hesperadin on brain edema, neurobehavioral function, and autophagy.
Main Methods:
- Mice were divided into sham, sham+hesperidin, ICH, and ICH+hesperadin groups.
- Brain edema and neurobehavioral function were evaluated.
- Western blotting and immunofluorescence were used to analyze MST4, AKT, pAKT, and LC3 expression and localization.
Main Results:
- Hesperadin treatment significantly reduced brain edema and improved neurological function in ICH mice.
- Hesperadin modulated MST4 and pAKT levels, suggesting pathway inhibition.
- Hesperadin decreased the increased autophagy observed in the ICH group.
Conclusions:
- Hesperadin demonstrates significant neuroprotection against ICH in a mouse model.
- The MST4/AKT signaling pathway is a key target for hesperadin's therapeutic effects.
- Hesperadin may represent a novel therapeutic strategy for treating intracerebral hemorrhage.
