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Updated: May 16, 2026

Rat Model of Closed-Head Mild Traumatic Injury and its Validation
Published on: September 22, 2023
The evolution of traumatic brain injury in a rat focal contusion model
L Christine Turtzo1, Matthew D Budde, Eric M Gold
1Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Frank Laboratory, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Serial MRI facilitates the in vivo analysis of the intra- and intersubject evolution of traumatic brain injury lesions. Despite the availability of MRI, the natural history of experimental focal contusion lesions in the controlled cortical impact (CCI) rat model has not been well described. We performed CCI on rats and MRI during the acute to chronic stages of cerebral injury to investigate the time course of changes in the brain. Female Wistar rats underwent CCI of their left motor cortex with a flat impact tip driven by an electromagnetic piston. In vivo MRI was performed at 7 T serially over 6 weeks post-CCI. The appearances of CCI-induced lesions and lesion-associated cortical volumes were variable on MRI, with the percentage change in cortical volume of the CCI ipsilateral side relative to the contralateral side ranging from 18% within 2 h of injury on day 0 to a peak of 35% on day 1, and a trough of -28% by week 5/6, with an average standard deviation of ± 14% at any given time point. In contrast, the percentage change in cortical volume of the ipsilateral side relative to the contralateral side in control rats was not significant (1 ± 2%). Hemorrhagic conversion within and surrounding the CCI lesion occurred between days 2 and 9 in 45% of rats, with no hemorrhage noted on the initial scan. Furthermore, hemorrhage and hemosiderin within the lesion were positive for Prussian blue and highly autofluorescent on histological examination. Although some variation in injuries may be technique related, the divergence of similar lesions between initial and final scans demonstrates the inherent biological variability of the CCI rat model.
Insights
Serial MRI reveals significant variability in traumatic brain injury lesion evolution in the controlled cortical impact (CCI) rat model. This study details the time course of lesion changes and highlights the inherent biological variability in this model.
Area of Science:
- Neuroscience
- Medical Imaging
- Animal Models
Background:
- Traumatic brain injury (TBI) lesion evolution requires in vivo analysis.
- The natural history of controlled cortical impact (CCI) lesions in rats is not well-characterized.
- Serial Magnetic Resonance Imaging (MRI) can track TBI progression.
Purpose of the Study:
- To investigate the time course of cerebral injury evolution in the CCI rat model using serial MRI.
- To describe the variability of lesion appearance and volume changes post-CCI.
- To characterize hemorrhagic conversion within TBI lesions.
Main Methods:
- Female Wistar rats underwent controlled cortical impact (CCI) to the motor cortex.
- In vivo MRI at 7 Tesla was performed serially over 6 weeks post-CCI.
- Histological examination, including Prussian blue staining, was used to identify hemorrhage and hemosiderin.
Main Results:
- CCI lesions showed variable MRI appearances and cortical volume changes (18% to 35% increase, -28% decrease by week 6).
- Hemorrhagic conversion occurred in 45% of rats between days 2-9 post-injury.
- Histology confirmed hemorrhage and hemosiderin, with significant biological variability observed between similar lesions.
Conclusions:
- Serial MRI effectively visualizes the dynamic changes in TBI lesions over time.
- The CCI rat model exhibits significant inherent biological variability in lesion development and progression.
- Understanding this variability is crucial for interpreting experimental TBI research.
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