Plasma Lipid Profiles Change with Increasing Numbers of Mild Traumatic Brain Injuries in Rats

Anyaegbu, Chidozie C.; Szemray, Harrison; Hellewell, Sarah C.; Lawler, Nathan G.; Leggett, Kerry; Bartlett, Carole A.; Lins, Brittney R.; McGonigle, Terence; Papini, Melissa; Anderton, Ryan S.; Whiley, Luke; Fitzgerald, Melinda

doi:10.3390/metabo12040322

Cited by 4 publications

(4 citation statements)

References 51 publications

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“…In pre-clinical TBI models, plasma lipid composition is altered with repetitive impacts in rats, which could be a consequence of active modulation of lipid content to match their roles in the dynamic processes of neurological recovery after repetitive brain trauma (Anyaegbu et al, 2022). For example, within 4 h of experimental TBI, there is an increase in both pro-and anti-inflammatory oxidized free et al, 2021).…”

Section: Tb I D Is Rup Ts Mi Crog Lial Lipid Me Tabolis M and In Cre ...mentioning

confidence: 99%

“…This may indicate that post‐traumatic lipid changes are an organized metabolic response that can contribute, along with other factors, to diverse clinical outcomes (Huguenard et al, 2020). In pre‐clinical TBI models, plasma lipid composition is altered with repetitive impacts in rats, which could be a consequence of active modulation of lipid content to match their roles in the dynamic processes of neurological recovery after repetitive brain trauma (Anyaegbu et al, 2022). For example, within 4 h of experimental TBI, there is an increase in both pro‐ and anti‐inflammatory oxidized free FA, particularly products of lipoxygenation by LOX‐15, whereas at 24 h post‐injury, only anti‐inflammatory FA are observed (Anthonymuthu et al, 2017).…”

Section: Tbi Disrupts Microglial Lipid Metabolism and Increases Keton...mentioning

confidence: 99%

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Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

Strogulski,

Portela,

Polster

et al. 2023

Journal of Neurochemistry

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Traumatic brain injury (TBI) is a devastating neurological disorder caused by a physical impact to the brain that promotes diffuse damage and chronic neurodegeneration. Key mechanisms believed to support secondary brain injury include mitochondrial dysfunction and chronic neuroinflammation. Microglia and brain‐infiltrating macrophages are responsible for neuroinflammatory cytokine and reactive oxygen species (ROS) production after TBI. Their production is associated with loss of homeostatic microglial functions such as immunosurveillance, phagocytosis, and immune resolution. Beyond providing energy support, mitochondrial metabolic pathways reprogram the pro‐ and anti‐inflammatory machinery in immune cells, providing a critical immunometabolic axis capable of regulating immunologic response to noxious stimuli. In the brain, the capacity to adapt to different environmental stimuli derives, in part, from microglia's ability to recognize and respond to changes in extracellular and intracellular metabolite levels. This capacity is met by an equally plastic metabolism, capable of altering immune function. Microglial pro‐inflammatory activation is associated with decreased mitochondrial respiration, whereas anti‐inflammatory microglial polarization is supported by increased oxidative metabolism. These metabolic adaptations contribute to neuroimmune responses, placing mitochondria as a central regulator of post‐traumatic neuroinflammation. Although it is established that profound neurometabolic changes occur following TBI, key questions related to metabolic shifts in microglia remain unresolved. These include (a) the nature of microglial mitochondrial dysfunction after TBI, (b) the hierarchical positions of different metabolic pathways such as glycolysis, pentose phosphate pathway, glutaminolysis, and lipid oxidation during secondary injury and recovery, and (c) how immunometabolism alters microglial phenotypes, culminating in chronic non‐resolving neuroinflammation. In this basic neurochemistry review article, we describe the contributions of immunometabolism to TBI, detail primary evidence of mitochondrial dysfunction and metabolic impairments in microglia and macrophages, discuss how major metabolic pathways contribute to post‐traumatic neuroinflammation, and set out future directions toward advancing immunometabolic phenotyping in TBI.image

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Section: Tb I D Is Rup Ts Mi Crog Lial Lipid Me Tabolis M and In Cre ...mentioning

confidence: 99%

Section: Tbi Disrupts Microglial Lipid Metabolism and Increases Keton...mentioning

confidence: 99%

Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

Strogulski,

Portela,

Polster

et al. 2023

Journal of Neurochemistry

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“…Studies using mass spectrometry have shown an increase in pro-inflammatory lipids such as bioactive lipids and lysophospholipids, which is consistent with post-TBI neuroinflammation. − Phospholipids are major constituents of the plasma membrane, and because TBI has been shown to cause membrane disruption, it follows that phospholipid dysregulation may be part of the injury process. Previous groups have reported significant changes of phospholipid species in single and repetitive TBI models. − Specifically, an increase in total phospholipids in the cortex hippocampus was demonstrated in the chronic phase post-TBI . Previous studies from our group have identified a 26-serum lipid panel that differentiates moderate TBI and sham control 3- and 7-days post injury .…”

Section: Introductionmentioning

confidence: 99%

Comparing Brain and Blood Lipidome Changes following Single and Repetitive Mild Traumatic Brain Injury in Rats

Pulliam,

Gier,

Gaul

et al. 2024

ACS Chem. Neurosci.

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Traumatic brain injury (TBI) is a major health concern in the United States and globally, contributing to disability and long-term neurological problems. Lipid dysregulation after TBI is underexplored, and a better understanding of lipid turnover and degradation could point to novel biomarker candidates and therapeutic targets. Here, we investigated overlapping lipidome changes in the brain and blood using a data-driven discovery approach to understand lipid alterations in the brain and serum compartments acutely following mild TBI (mTBI) and the potential efflux of brain lipids to peripheral blood. The cortices and sera from male and female Sprague−Dawley rats were analyzed via ultra-high performance liquid chromatography−mass spectrometry (UHPLC-MS) in both positive and negative ion modes following single and repetitive closed head impacts. The overlapping lipids in the data sets were identified with an in-house data dictionary for investigating lipid class changes. MS-based lipid profiling revealed overall increased changes in the serum compartment, while the brain lipids primarily showed decreased changes. Interestingly, there were prominent alterations in the sphingolipid class in the brain and blood compartments after single and repetitive injury, which may suggest efflux of brain sphingolipids into the blood after TBI. Genetic algorithms were used for predictive panel selection to classify injured and control samples with high sensitivity and specificity. These overlapping lipid panels primarily mapped to the glycerophospholipid metabolism pathway with Benjamini−Hochberg adjusted q-values less than 0.05. Collectively, these results detail overlapping lipidome changes following mTBI in the brain and blood compartments, increasing our understanding of TBIrelated lipid dysregulation while identifying novel biomarker candidates.

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“…Examples of lipids that may be implicated in mTBI include phosphatidylethanolamine (PE), Bis(monoacylglycero)phosphate (BMP), acylcarnitine (AC & AC-OH), cardiolipin (CL), lysophosphatidylcholines (LPC), lysophosphatidylethanolamine (LPE), and lysophosphatidylinositol (LPI). PE is a major component of cell membranes that is implicated in membrane stability, trafficking, permeability, and fluidity ( Yoon et al, 2022 ), and it has also been linked to neurodegenerative disorders ( Anyaegbu et al, 2022 ). BMP is enriched in the lysosomal network and is suspected to represent a biomarker of phagocytizing macrophages/microglia in brain tissue and is implicated in various physiological cellular functions, such as cell signaling and the regulation of neuronal growth ( Nielsen et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Acute effects of single and repeated mild traumatic brain injury on levels of neurometabolites, lipids, and mitochondrial function in male rats

Allen

Pham

Bond

et al. 2023

Front. Mol. Neurosci.

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IntroductionMild traumatic brain injuries (mTBIs) are the most common form of acquired brain injury. Symptoms of mTBI are thought to be associated with a neuropathological cascade, potentially involving the dysregulation of neurometabolites, lipids, and mitochondrial bioenergetics. Such alterations may play a role in the period of enhanced vulnerability that occurs after mTBI, such that a second mTBI will exacerbate neuropathology. However, it is unclear whether mTBI-induced alterations in neurometabolites and lipids that are involved in energy metabolism and other important cellular functions are exacerbated by repeat mTBI, and if such alterations are associated with mitochondrial dysfunction.MethodsIn this experiment, using a well-established awake-closed head injury (ACHI) paradigm to model mTBI, male rats were subjected to a single injury, or five injuries delivered 1 day apart, and injuries were confirmed with a beam-walk task and a video observation protocol. Abundance of several neurometabolites was evaluated 24 h post-final injury in the ipsilateral and contralateral hippocampus using in vivo proton magnetic resonance spectroscopy (1H-MRS), and mitochondrial bioenergetics were evaluated 30 h post-final injury, or at 24 h in place of 1H-MRS, in the rostral half of the ipsilateral hippocampus. Lipidomic evaluations were conducted in the ipsilateral hippocampus and cortex.ResultsWe found that behavioral deficits in the beam task persisted 1- and 4 h after the final injury in rats that received repetitive mTBIs, and this was paralleled by an increase and decrease in hippocampal glutamine and glucose, respectively, whereas a single mTBI had no effect on sensorimotor and metabolic measurements. No group differences were observed in lipid levels and mitochondrial bioenergetics in the hippocampus, although some lipids were altered in the cortex after repeated mTBI.DiscussionThe decrease in performance in sensorimotor tests and the presence of more neurometabolic and lipidomic abnormalities, after repeated but not singular mTBI, indicates that multiple concussions in short succession can have cumulative effects. Further preclinical research efforts are required to understand the underlying mechanisms that drive these alterations to establish biomarkers and inform treatment strategies to improve patient outcomes.

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Plasma Lipid Profiles Change with Increasing Numbers of Mild Traumatic Brain Injuries in Rats

Cited by 4 publications

References 51 publications

Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

Comparing Brain and Blood Lipidome Changes following Single and Repetitive Mild Traumatic Brain Injury in Rats

Acute effects of single and repeated mild traumatic brain injury on levels of neurometabolites, lipids, and mitochondrial function in male rats

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