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Updated: Jun 1, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Activation of JAK2/STAT pathway in cerebral cortex after experimental traumatic brain injury of rats
Jin-bing Zhao1, Yang Zhang, Guang-zhao Li
1Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu Province, PR China.
Abstract:
The janus kinase/signal transducer and activator of transcription (JAK/STAT) is one of the main pathways downstream of cytokine receptors and growth factor receptors by transducing signals from cell surface to the nucleus. In this study, we aimed to survey the role of JAK2/STAT pathway in the progress of TBI. Right parietal cortical contusion in rats was induced by the Feeney free falling model. The activation of JAK2, STAT1 and STAT3 in pericontusional cortex was determined by Western blotting, electrophoretic mobility shift assay (EMSA), immunohistochemistry and immunofluorescence. Moreover, we assessed the neurological recovery (using Neurological Severity Scores (NSS)) of rats under the pretreatment of a JAK2 inhibitor, AG490. Western blotting revealed that expression of p-JAK2, p-STAT1 and p-STAT3 increased immediately, peaked at 3h after TBI and decreased thereafter, and the activation could be inhibited by AG490. Immunohistochemical study showed that JAK2/STAT pathway was activated in both neurons and astrocytes at 3h after TBI. STAT3-specific binding activity was obviously enhanced after TBI and down-regulated after AG490 administration. The higher NSS of TBI+AG490 group revealed a worse behavior recovery when compared with TBI+DMSO group. Our results suggest that the JAK2/STAT pathway is activated in pericontusional cortex of rats, and may be involved in the neurological function recovery after TBI.
Insights
The janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is activated after traumatic brain injury (TBI). Inhibiting this pathway worsened neurological recovery in rats, suggesting its role in TBI healing.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- The Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway is crucial for cellular signaling downstream of cytokine and growth factor receptors.
- Understanding the role of intracellular signaling pathways in the acute phase of traumatic brain injury (TBI) is essential for developing effective treatments.
Purpose of the Study:
- To investigate the involvement of the JAK2/STAT pathway in the progression of TBI.
- To evaluate the effect of JAK2 inhibition on neurological recovery following TBI.
Main Methods:
- Traumatic brain injury (TBI) was induced in rats using the Feeney free falling model.
- JAK2/STAT pathway activation was assessed using Western blotting, electrophoretic mobility shift assay (EMSA), immunohistochemistry, and immunofluorescence.
- Neurological recovery was evaluated using the Neurological Severity Scores (NSS) in rats pretreated with the JAK2 inhibitor AG490.
Main Results:
- Expression of phosphorylated JAK2, STAT1, and STAT3 increased post-TBI, peaking at 3 hours, and was inhibited by AG490.
- Immunohistochemistry revealed JAK2/STAT pathway activation in both neurons and astrocytes at 3 hours post-TBI.
- STAT3 DNA binding activity was enhanced after TBI and reduced by AG490; rats treated with AG490 exhibited worse neurological recovery (higher NSS).
Conclusions:
- The JAK2/STAT pathway is activated in the pericontusional cortex following TBI in rats.
- This pathway appears to play a role in neurological function recovery after TBI.
- Targeting the JAK2/STAT pathway may represent a potential therapeutic strategy for TBI, although further investigation is warranted.
