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Updated: Aug 7, 2026
Optimized System for Cerebral Perfusion Monitoring in the Rat Stroke Model of Intraluminal Middle Cerebral Artery Occlusion
Published on: February 17, 2013
c-Jun N-terminal kinase (JNK) and JNK interacting protein response in rat brain after transient middle cerebral
1Department of Neurology, Okayama University Medical School, 2-5-1 Shikata-machi, 700-8558, Okayama, Japan. thayashi@cc.okayama-u.ac.jp
Abstract:
c-Jun response is involved in the development of ischemic brain injury, which is activated by c-Jun N-terminal kinase-1 (JNK-1). The activity of JNK-1 is strictly regulated, and only the phosphorylated form of JNK (phospho-JNK) which is translocated to the nucleus has an ability to activate c-Jun response. There is a protein which inhibits JNK-1 activation, and known as JNK interacting protein-1 (JIP-1). In this study, we investigated change in JNK-1, phospho-JNK, and JIP-1 immunoreactivity in rat brain after transient middle cerebral artery (MCA) occlusion. Immunoreactive JNK-1 was scant in the sham-control brain, but it was induced at 1 h after reperfusion, which was slightly increased at 3 h of reperfusion. By contrast, phospho-JNK remained negative till 3 h. At 8 h, JNK-1 and phospho-JNK became distinctly positive, and nuclei as well as cytoplasm were stained. Thereafter, immunoreactivity for JNK-1 and phospho-JNK became furthermore dense, and most neurons revealed positively stained nuclei. Immunoreactivity for JIP-1 remained negative till 8 h of reperfusion, but at 24 and 72 h, cytoplasm of cortical neurons at the MCA boundary area was positively stained. This JIP-1 induction got behind the JNK-1 activation, and therefore, may be a vain effort for neurons to survive. Inhibition of JNK-1 activation might become an innovative means of therapy for stroke treatment in the future.
Insights
c-Jun N-terminal kinase-1 (JNK-1) activation is key in ischemic brain injury. JNK-1 and its phosphorylated form increase after stroke, while JNK interacting protein-1 (JIP-1) rises later, suggesting a potentially ineffective survival response.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Ischemic brain injury involves c-Jun response, activated by c-Jun N-terminal kinase-1 (JNK-1).
- JNK-1 activity is regulated by phosphorylation and nuclear translocation, with JNK interacting protein-1 (JIP-1) inhibiting its activation.
- Understanding these molecular events is crucial for developing stroke therapies.
Purpose of the Study:
- To investigate the temporal changes in JNK-1, phospho-JNK, and JIP-1 immunoreactivity in a rat model of transient middle cerebral artery (MCA) occlusion.
- To elucidate the role of JIP-1 in the context of JNK-1 activation following ischemic stroke.
Main Methods:
- Transient middle cerebral artery (MCA) occlusion model in rats.
- Immunohistochemical analysis of JNK-1, phospho-JNK, and JIP-1 expression at various time points post-reperfusion.
- Assessment of protein localization within neuronal compartments (cytoplasm and nucleus).
Main Results:
- JNK-1 and phospho-JNK immunoreactivity increased significantly from 8 hours to 72 hours post-reperfusion, with nuclear and cytoplasmic staining observed.
- JIP-1 immunoreactivity remained negative until 8 hours, becoming positive in cortical neurons at 24 and 72 hours post-reperfusion.
- JIP-1 induction lagged behind JNK-1 activation, suggesting a delayed and potentially insufficient protective response.
Conclusions:
- The delayed induction of JIP-1 after JNK-1 activation in ischemic stroke may represent a futile attempt by neurons to survive.
- Targeting JNK-1 activation could offer a novel therapeutic strategy for treating stroke.
- Further research into the precise mechanisms of JNK-1 regulation and JIP-1 interaction is warranted.
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