Article
Inflammatory changes in the hippocampus after experimental traumatic brain injury in a rat model
Entzündliche Veränderungen im Hippocampus nach experimentellem Schädel-Hirn-Trauma in einem Rattenmodell
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Authors
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Karin Große
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Martin Grutza
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Johannes Walter
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Stefan Heene
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Guoli Zheng
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Thomas Skutella
- Universitätsklinikum Heidelberg, Neuroanatomie, Heidelberg, Deutschland
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Andreas W. Unterberg
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Klaus Zweckberger
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
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Alexander Younsi
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Traumatic brain injury (TBI) is a leading cause of death worldwide. After the primary injury, a cascade of secondary injury processes is initiated, including a complex inflammatory reaction. As a critical and vulnerable brain region, the hippocampus is commonly affected by such neuroinflammation. However, the detailed inflammatory changes in the hippocampus after TBI are not yet completely understood. Therefore, we used an experimental TBI model in rats to examine potential inflammatory mechanisms and pathways in the hippocampus.
Methods: A right parietal controlled cortical impact (CCI) or sham surgery (craniotomy only) was performed in 84 male Wistar rats. Behavioral changes were assessed via the open-field test 24 h, 72 h, 7 d, 14 d, and 28 d after CCI. To depict the course of inflammatory mechanisms and pathways, animals were sacrificed 15 min, 24 h, 72 h, 7 d, 14 d and 28 d after CCI. The brains were removed, frozen and a 4 x 4 x 1 mm area centered around the hippocampus was resected for western blot (WB) and quantitative real-time PCR (qPCR) analyses. Results were statistically compared between groups (CCI, sham) and timepoints (p < 0.05 was considered significant).
Results: Injured animals showed significantly increased motor deficits 24 h, 72 h and 7 days post-surgery as well as significantly increased anxiety-like and exploratory behavior 7 days and 28 days after CCI compared to sham animals in the open-field test. The qPCR results indicated several relevant gene expression changes associated with an amplified and prolonged inflammatory reaction in CCI animals. This modulation of inflammatory pathways was also reflected in markedly increased inflammatory protein expression levels, detected via WB: Inter alia, differences of TNF-alpha, IL-1beta, TGF-beta, GFAP, iNos, Iba1, CD16 and CD206 could be detected between the injured CCI and the uninjured sham animals.
Conclusion: Our results contribute to an expanded understanding of secondary inflammatory changes in the hippocampus after experimental TBI. Modulation of inflammatory mechanisms and pathways might mediate neuroprotective effects. Thus, the current findings might enable further investigations to develop experimental treatments for TBI in the future.
