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Updated: May 8, 2026
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
The pCREB/BDNF Pathway in the Hippocampus Is Involved in the Therapeutic Effect of Selective 5-HT Reuptake Inhibitors
Xiaolin Fan1,2, Hong Wang2, Xiaoqiang Lv2
1Laboratory for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, No. 127 Youyi West Road, Beilin District, Xi'an 710072, China.
Background:
Blast traumatic brain injury (bTBI) can result in depression-like behaviors in the acute and chronic phases. SSRIs have been shown to significantly alleviate depression-like behaviors in animal models of traumatic brain injury (TBI) by increasing serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. However, the therapeutic effects of SSRIs on depression caused by bTBI remain unclear.
Objective:
Therefore, this study was aimed at investigating the therapeutic effects of SSRIs on depression-like behaviors in bTBI models.
Methods:
We created a rat model to study mild TBI by subjecting rats to increased blast overpressures (BOP) and injecting fluoxetine and escitalopram SSRIs intraperitoneally for 28 days.
Results:
On day 14 post-BOP exposure, rats treated with SSRIs showed decreased depression-like behaviors. This finding was accompanied by higher 5-HT levels in the hippocampus and increased numbers of Nestin-positive cells in the dentate gyrus. Furthermore, rats treated with SSRIs exhibited increased pCREB and BDNF protein expression in the hippocampus on days 7, 14, and 28 after bTBI.
Conclusions:
Overall, our findings indicate that SSRI-induced recovery from depression-like behaviors after mild bTBI is associated with the upregulation of 5-HT levels, pCREB and BDNF expression, and neurogenesis in the hippocampus.
