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Updated: Oct 3, 2025
Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Hippocampal Activated Microglia May Contribute to Blood-Brain Barrier Impairment and Cognitive Dysfunction in
Kun Ni1, Jixiang Zhu1, Xuan Xu1
1Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, China.
Abstract:
Post-traumatic stress disorder (PTSD)-associated cognitive dysfunction significantly disturbs patients' quality of life and will to live. However, its underlying mechanism is as yet unknown. Recent researches indicate that blood-brain barrier (BBB) breakdown is responsible for early cognitive dysfunction. Microglia might participate in remodeling of BBB-associated tight junction and regulating BBB integrity. Nevertheless, it is unclear whether microglia activation and BBB injury involve in PTSD-associated cognitive dysfunction. Hence, we established an animal model of PTSD, single prolonged stress (SPS), and investigated permeability changes in the hippocampus and further explored the effects of microglia on BBB remodeling. The Y maze was used to assess the changes of cognitive function. The sodium fluorescein (NaFlu) assay and western blotting analysis were employed to detect BBB integrity changes. Minocycline was administered to inhibit microglial activation. Immunofluorescence stains were used to assess the activation states in microglia. The results showed that SPS-exposed rats exhibited poorer cognitive performance, higher passage of NaFlu, and lower expression of tight junction proteins (occludin and claudin 5) in the hippocampus on the day after SPS, but no difference on the 7th day. Inhibition of microglial activation by minocycline attenuated poor cognitive performance and BBB impairment including the extravasation of NaFlu and protein levels of the tight junction. Taken together, the present study indicates that BBB impairment may underlie the shared pathological basis of PTSD and cognitive dysfunction. Microglial activation may involve in BBB remodeling at the early stage of SPS.
Insights
Post-traumatic stress disorder (PTSD) impairs cognitive function early on due to blood-brain barrier (BBB) breakdown. Microglia activation contributes to this BBB damage and cognitive deficits in a rat model.
Area of Science:
- Neuroscience
- Pathology
- Pharmacology
Background:
- Post-traumatic stress disorder (PTSD) is linked to cognitive dysfunction, impacting quality of life.
- The exact mechanisms behind PTSD-associated cognitive impairment remain unclear.
- Emerging evidence suggests blood-brain barrier (BBB) dysfunction contributes to early cognitive deficits.
Purpose of the Study:
- To investigate the role of microglia in BBB remodeling and cognitive dysfunction in an animal model of PTSD.
- To explore the relationship between BBB integrity, microglial activation, and cognitive performance following single prolonged stress (SPS).
Main Methods:
- Established a single prolonged stress (SPS) rat model to mimic PTSD.
- Assessed cognitive function using the Y-maze test.
- Evaluated BBB integrity via sodium fluorescein (NaFlu) assay and Western blotting for tight junction proteins (occludin, claudin 5).
- Administered minocycline to inhibit microglial activation and assessed its effects.
Main Results:
- SPS-induced rats showed impaired cognitive performance and increased BBB permeability (NaFlu passage) in the hippocampus.
- Reduced expression of tight junction proteins (occludin, claudin 5) was observed in the hippocampus post-SPS.
- Minocycline treatment attenuated cognitive deficits and mitigated BBB impairment, including reduced NaFlu extravasation and normalized tight junction protein levels.
- These effects were most pronounced on the day after SPS, with less difference noted by the 7th day.
Conclusions:
- Blood-brain barrier (BBB) impairment is implicated in the pathology of PTSD-associated cognitive dysfunction.
- Microglial activation plays a significant role in BBB remodeling and exacerbating cognitive deficits during the early stages of SPS-induced PTSD.
- Targeting microglial activation may offer a therapeutic strategy for mitigating cognitive impairments in PTSD.
