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Updated: Jun 21, 2025
A Pediatric Concussion Model in Mice: Closed Head Injury with Long-Term Disorders (CHILD)
Published on: February 7, 2025
High-fat diet consumption negatively influences closed-head traumatic brain injury in a pediatric rodent model
Allie M Smith1, Trenton J Ray1, Alicia A Hulitt1
1Department of Neurology, University of Mississippi Medical Center, Jackson, MS 39216, United States of America.
Insights
A high-fat, high-fructose corn syrup diet exacerbates cognitive and cerebrovascular impairments following traumatic brain injury (TBI) in juvenile rats. This diet negatively impacts recovery and brain function after TBI.
Area of Science:
- Neuroscience
- Pediatric Injury Research
- Nutritional Science
Background:
- Traumatic brain injury (TBI) is a leading cause of death and disability in children.
- Obesity and high-fat diets are prevalent in pediatric populations, potentially influencing TBI outcomes.
- Juvenile rats exposed to a high-fat, high-fructose corn syrup (HFD/HFCS) diet exhibit cognitive and cerebrovascular changes post-TBI.
Purpose of the Study:
- To investigate the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats.
- To assess how a HFD/HFCS diet affects TBI-induced changes in learning, memory, and brain blood flow.
- To determine the molecular and cellular responses in the brain following TBI in rats fed a standard or HFD/HFCS diet.
Main Methods:
- Juvenile male Long Evans rats were fed either a standard chow or HFD/HFCS diet for 9 days before undergoing mild TBI using the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or sham procedures.
- Cognitive function was assessed using the Morris water maze pre- and post-injury.
- Cerebrovascular perfusion was measured using Laser Speckle, and brain tissues were analyzed via qRT-PCR and immunohistochemistry for molecular and cellular markers.
Main Results:
- TBI significantly impaired righting reflexes and short-term cognitive performance in the Morris water maze, irrespective of diet.
- HFD/HFCS-fed rats exhibited reduced cerebrovascular blood flow in the cerebellum and decreased RECA staining in the cortex and corpus callosum post-TBI.
- Gene expression analysis revealed significant upregulation of inflammatory and neuronal markers (APOE, CREB1, FCGR2B, IL1B, IL6) in the hippocampus of TBI rats, particularly those on the HFD/HFCS diet.
Conclusions:
- A HFD/HFCS diet worsens cognitive deficits and cerebrovascular impairments following TBI in juvenile rats.
- Dietary factors play a critical role in TBI outcomes, influencing brain function and recovery.
- These findings highlight the importance of diet in mitigating TBI-related damage in pediatric populations.
Abstract:
Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets that are high in saturated fats, and millions of children are overweight or obese. The goal of the present study was to assess the relationship between diet and TBI on cognitive and cerebrovascular outcomes in juvenile rats. In the current study, groups of juvenile male Long Evans rats were subjected to either mild TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or underwent sham procedures. The animals were provided with either a combination of high-fat diet and a mixture of high-fructose corn syrup (HFD/HFCS) or a standard chow diet (CH) for 9 days prior to injury. Prior to injury, the animals were trained on the Morris water maze for three consecutive days, and they underwent a post-injury trial on the day of the injury. Immediately after TBI, the animals' righting reflexes were tested. Four days post-injury, the animals were euthanized, and brain samples and blood plasma were collected for qRT-PCR, immunohistochemistry, and triglyceride assays. Additional subsets of animals were used to investigate cerebrovascular perfusion using Laser Speckle and perform immunohistochemistry for endothelial cell marker RECA. Following TBI, the righting reflex was significantly increased in TBI rats, irrespective of diet. The TBI worsened the rats' performance in the post-injury trial of the water maze at 3 h, p(injury) < 0.05, but not at 4 days post-injury. Reduced cerebrovascular blood flow using Laser Speckle was demonstrated in the cerebellum, p(injury) < 0.05, but not foci of the cerebral cortices or superior sagittal sinus. Immunoreactive staining for RECA in the cortex and corpus callosum was significantly reduced in HFD/HFCS TBI rats, p < 0.05. qRT-PCR showed significant increases in APOE, CREB1, FCGR2B, IL1B, and IL6, particularly in the hippocampus. The results from this study offer robust evidence that HFD/HFCS negatively influences TBI outcomes with respect to cognition and cerebrovascular perfusion of relevant brain regions in the juvenile rat.
