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Published on: January 20, 2023
Multimodal Magnetic Resonance Imaging with Mild Repetitive Head Injury in Awake Rats: Modeling the Human Experience
Nicole Bens1, Arnold Chang1, Richard Ortiz2
1Center for Translational Neuroimaging, Northeastern University, Boston, MA, 02115, USA.
Abstract:
Mild repetitive head injury is a serious health problem with long-term negative consequences. Changes in brain neurobiology were assessed with MRI in a model of head injury designed to reflect the human experience. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days while fully awake under red light illumination. There was no neuroradiological evidence of brain damage. Rats were imaged for changes in blood brain barrier permeability, edema and gray matter microarchitecture, and resting state functional connectivity. Data were registered to a 3D MRI rat atlas with 173 segmented brain areas providing site-specific information on each imaging modality. Changes in BBB permeability were minimal and localized to the hippocampus and cerebellum. There was evidence of cytotoxic edema in the basal ganglia, thalamus, and cerebellum. There was a global decrease in connectivity and an increase in gliosis in the thalamus, cerebellum, and hippocampus. This study shows a sequelae of neuropathology caused by mild repetitive head injury that is commonly observed in clinical practice using MRI in patients. As such, it may serve as a model for testing the efficacy of new therapeutics using any or all of the measures as biomarkers to assess drug efficacy.
Insights
Mild repetitive head injury causes subtle brain changes, including altered connectivity and swelling, detectable by MRI. This rat model may help test new treatments for head injury neuropathology.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Radiology
Background:
- Mild repetitive head injury (RHI) presents significant long-term health challenges.
- Understanding RHI's neurobiological impact is crucial for effective treatment development.
- Current clinical imaging often misses subtle RHI-induced brain alterations.
Purpose of the Study:
- To investigate the neurobiological consequences of mild RHI in a rat model.
- To assess changes in blood-brain barrier (BBB) permeability, edema, and functional connectivity using MRI.
- To establish a preclinical model for evaluating therapeutic interventions for RHI.
Main Methods:
- Rats underwent daily head impacts for three days under controlled conditions.
- Magnetic Resonance Imaging (MRI) was used to evaluate BBB permeability, edema, and resting-state functional connectivity.
- Imaging data were registered to a 3D MRI rat atlas for precise localization of changes.
Main Results:
- No gross neuroradiological damage was observed.
- Minimal BBB permeability changes were localized to the hippocampus and cerebellum.
- Cytotoxic edema was detected in the basal ganglia, thalamus, and cerebellum.
- Global decrease in functional connectivity and increased gliosis in the thalamus, cerebellum, and hippocampus were noted.
Conclusions:
- Mild RHI induces a pattern of neuropathology, including edema and altered connectivity, mirroring human clinical observations.
- The identified MRI-based biomarkers (BBB permeability, edema, connectivity) can be utilized in this model.
- This study provides a valuable preclinical model for assessing the efficacy of novel therapeutics for RHI.
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