High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury

Ibeh, Stanley; Bakkar, Nour-Mounira Z.; Faraz, Ahmad; Nwaiwu, Judith; Barsa, Chloe; Mekhjian, Sarine; Reslan, Mohammad Amine; Eid, Ali H.; Harati, Hayat; Nabha, Sanaa; Mechref, Yehia; El‐Yazbi, Ahmed F.; Kobeissy, Firas

doi:10.1016/j.lfs.2022.121316

Cited by 7 publications

(5 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 82 ] Similarly, a high-fat diet (HFD) showed an impact on the outcomes of TBI in an experimental mouse model. [ 44 ] The mice were fed an HFD for two months and subjected to control cortical impact-induced TBI. The results revealed that the combination of TBI and HFD led to significant metabolic, neurological, and behavioral impairments.…”

Section: Lifestyle-based Interventionsmentioning

confidence: 99%

The importance of behavioral interventions in traumatic brain injury

Buccilli,

Alan,

Baha’

et al. 2024

Surgical Neurology International

View full text Add to dashboard Cite

Background: Traumatic brain injury (TBI) poses a significant public health concern, profoundly impacting individuals and society. In this context, behavioral interventions have gained prominence as crucial elements in TBI management, addressing the diverse needs of TBI-affected individuals. Methods: A comprehensive literature search was conducted, utilizing databases such as PubMed, Embase, and Scopus. Inclusion criteria encompassed studies focusing on behavioral interventions in TBI, with a particular emphasis on their impact on outcomes. Relevant articles published within the past decade were prioritized, and a qualitative synthesis of the findings was performed. Results: Behavioral interventions have demonstrated their effectiveness in addressing various aspects of TBI care. They have been instrumental in improving cognitive functions, emotional stability, and adaptive behaviors among TBI patients. However, it is important to acknowledge that challenges still exist, including issues related to clinical heterogeneity and healthcare disparities. Conclusion: The integration of behavioral interventions into standard clinical practice marks a transformative shift in TBI care. This approach holds immense potential for enhancing patient outcomes and elevating the overall quality of life for individuals grappling with the complexities of this condition. This review serves as a clarion call for healthcare practitioners, researchers, and policymakers to recognize the pivotal role of behavioral interventions in TBI care, advocating for their wider adoption to advance the field toward a more holistic and patient-centric approach.

show abstract

Section: Lifestyle-based Interventionsmentioning

confidence: 99%

The importance of behavioral interventions in traumatic brain injury

Buccilli,

Alan,

Baha’

et al. 2024

Surgical Neurology International

View full text Add to dashboard Cite

show abstract

“…Notably, evidence suggests that pre-existing diet-induced obesity is associated with an amplification of post-TBI pro-inflammatory responses and increased microglia-altered states in several brain regions [23][24][25]. Additional studies report dietinduced exacerbations in TBI-induced cognitive decline [24,25] and central (brain) insulin resistance [26].…”

Section: Introductionmentioning

confidence: 99%

“…Activation of brain and peripheral inflammation pathways is a key pathophysiological feature in both TBI [8][9][10][11][12] and obesity [12][13][14][15][16][17][18][19][20] and has been implicated in the development of associated neurological dysfunction [8,21,22]. Notably, evidence suggests that pre-existing diet-induced obesity is associated with an amplification of post-TBI pro-inflammatory responses and increased microglia-altered states in several brain regions [23][24][25]. Additional studies report dietinduced exacerbations in TBI-induced cognitive decline [24,25] and central (brain) insulin resistance [26].…”

Section: Introductionmentioning

confidence: 99%

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction

Henry

Barrett

Vaida

et al. 2023

Preprint

View full text Add to dashboard Cite

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). We performed a detailed analysis of transcriptomic changes in the brain and adipose tissue to examine the interactive effects between high-fat diet-induced obesity (DIO) and TBI in relation to central and peripheral inflammatory pathways, as well as neurological function. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. Combined TBI and HFD resulted in additive dysfunction in the Y-Maze, novel object recognition (NOR), and Morris water maze (MWM) cognitive function tests. We also performed high-throughput transcriptomic analysis using Nanostring panels of cellular compartments in the brain and total visceral adipose tissue (VAT), followed by unsupervised clustering, principal component analysis, and IPA pathway analysis to determine shifts in gene expression programs and molecular pathway activity. Analysis of cellular populations in the cortex and hippocampus as well as in visceral adipose tissue during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in select gene expression signatures and pathways. These data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and visceral adipose tissue macrophages, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue macrophages, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.

show abstract

“…Activation of brain and peripheral inflammation pathways is a key pathophysiological feature in both TBI [ 8 – 12 ] and obesity [ 12 – 20 ] and has been implicated in the development of associated neurological dysfunction [ 8 , 21 , 22 ]. Notably, evidence suggests that pre-existing diet-induced obesity is associated with an amplification of post-TBI pro-inflammatory responses and increased microglia-altered states in several brain regions [ 23 – 25 ]. Additional studies report diet-induced exacerbations in TBI-induced cognitive decline [ 24 , 25 ] and central (brain) insulin resistance [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Notably, evidence suggests that pre-existing diet-induced obesity is associated with an amplification of post-TBI pro-inflammatory responses and increased microglia-altered states in several brain regions [ 23 – 25 ]. Additional studies report diet-induced exacerbations in TBI-induced cognitive decline [ 24 , 25 ] and central (brain) insulin resistance [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction

Henry,

Barrett,

Vaida

et al. 2024

J Neuroinflammation

View full text Add to dashboard Cite

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction.

show abstract

High fat diet exacerbates long-term metabolic, neuropathological, and behavioral derangements in an experimental mouse model of traumatic brain injury

Cited by 7 publications

References 91 publications

The importance of behavioral interventions in traumatic brain injury

The importance of behavioral interventions in traumatic brain injury

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction

Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction

Contact Info

Product

Resources

About