Neuropathological Mechanisms of Mild Traumatic Brain Injury: A Perspective From Multimodal Magnetic Resonance Imaging

Liu, Yin; Lu, Liangliang; Li, Fengfang; Chen, Yu‐Chen

doi:10.3389/fnins.2022.923662

“…In moderate and severe TBI, multimodal imaging historically plays a greater role in prognostication and determining the need and appropriateness of aggressive interventions [ 175 , 176 ]. MRI has been studied in clinical trials, predominantly in mTBI in the subacute or chronic phase, as it is available in most academic medical centers and does not expose the patient to ionizing radiation [ 174 , 177 ]. MRI sequences, including diffusion weighted imaging (DWI), can be used to image cerebral edema following TBI, even in the first few days following injury [ 178 , 179 ], which could guide the early administration of therapies to reduce edema [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch

¹

,

Narayan

²

,

Li

³

2023

JCM

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

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“…TBI is a global public health problem that not only affects the long-term cognitive, physical, and mental health of patients, but also has a significant impact on families and caregivers 15 . Due to the lack of early imaging features in some mTBI patients, although mTBI patients have a history of brain trauma, it is often difficult to distinguish them from concussion, which often leads to delayed treatment and affects early treatment [16][17][18][19] . Therefore, biomarkers are needed to differentiate concussion from mTBI at an early stage in order to improve outcomes.…”

Section: Discussionmentioning

confidence: 99%

WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury

Liu,

Zhao,

Zheng

2023

Preprint

0

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BackgroundTraumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. However, there are no sensitive diagnostic or prognostic biomarkers to identify TBI, which leads to long-term consequences. In this study, we aim to identify genes that contribute to brain injury and to identify potential mechanisms for its progression in the early stages.MethodFrom the Gene Expression Omnibus (GEO) database, we downloaded GSE2871’s gene expression profiles. Weighted gene coexpression network analyses (WGCNA) were conducted on differentially expressed genes (DEGs), and the DEGs were analyzed by Gene Set Enrichment Analysis(GSEA). An enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed for understanding the biological functions of genes. The potential biomarkers were identified using 3 kinds of machine learning algorithms. Nomogram was constructed using the “rms” package. And the receiver operating characteristic curve (ROC) was plotted to detect and validate our prediction model sensitivity and specifificity.ResultsBetween samples with and without brain injury, 107 DEGs were identified, including 47 upregulated genes and 60 downregulated genes. On the basis of WGCNA and DEGs, 97 target genes were identified. In addition, biological function analysis indicated that target genes were primarily involved in the interaction of neuroactive ligands with receptors, taste transduction, cortisol synthesis and secretion, potassium ion transport. Based on machine learning algorithms, LOC103691092, Npw could be potentially useful biomarkers for TBI and showed good diagnostic values. Finally, a nomogram was constructed of the expression levels of these seven target genes to predict level of TBI, and the ROC showed that these genes can be used as hub genes after TBI.ConclusionLOC103691092, NPW, STK39, KCND3, APOC3, FOXE3, and CHRNB1 were identified as hub genes of TBI. These findings can provide a new direction for the diagnosis and treatment of TBI.

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“…In moderate and severe TBI multimodal imaging historically plays a greater role in prognostication and determining the need and approprateness of aggressive interventions [138,139]. Multimodal MRI has been studied in clinical trials, predominantly in mTBI in the subacute or chronic phase, as it is available in most academic medical centers and does not expose the patient to ionizing radation [137,140] MRI sequences including diffusion weighted imaging (DWI) can be used to image cerebral edema following TBI, even in the first few days following injury [141,142], which could guide the early administration of therapies to reduce edema [12]. Other advanced MRI sequences such as functional MRI (fMRI) and magnetic resonance specroscopy (MRS) may have a role in guiding treatment decisions after TBI.…”

Section: Imaging-and Neuromonitoring-guided Treatmentmentioning

confidence: 99%

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch¹,

Narayan²,

Li³

2023

Preprint

3

0

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

show abstract

Neuropathological Mechanisms of Mild Traumatic Brain Injury: A Perspective From Multimodal Magnetic Resonance Imaging

Cited by 5 publications

References 73 publications

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

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