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Neuropathology and Cellular Mechanisms in Traumatic Brain Injury 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6663

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Special Issue Editor

Dr. Firas Kobeissy

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Guest Editor

Center for Neurotrauma, Multiomics & Biomarkers, Department of Neurobiology & Neuroscience Institute, Morehouse School of Medicine (MSM), 720 Westview Drive, SW, Atlanta, GA 30310, USA
Interests: biological psychiatry; neuroscience, pharmacogenomics; brain injury, toxicology; substance abuse neurodegeneration; inflammation; antioxidants; multi-omics; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Traumatic brain injury (TBI) is a worldwide health problem leading to a series of complex, inter-related neurological and behavioral alterations that affect the brain and spinal cord. TBI presents a major socioeconomic burden, with an estimated 1.7 million civilians sustaining a TBI in the United States annually, with approximately 50,000 deaths and 200,000 moderate-to-severe injuries, resulting in ~USD 70 billion in hospitalization costs.

Over the last decade, neurotrauma has witnessed significant advances, especially at the molecular, cellular, and behavioral levels; however, there are no FDA-approved effective pharmacological treatments available due to the complex secondary injury cascades that involve neuroinflammation, glutamate toxicity, blood–brain barrier breach, lipid peroxidation, the release of reactive oxygen species (ROS), and mitochondrial dysfunction. These neuropathological outcomes create a predisposition to other neurodegenerative disorders, including Alzheimer’s disease, Parkinson's Disease, and chronic traumatic encephalopathy. Thus, there is a continual quest to decipher novel pathways, mechanisms, and biomarkers involved in brain injury pathology to achieve effective rehabilitation and neuroprotective strategies.

This Special Issue invites researchers and clinicians to discuss neurotrauma mechanisms, biomarker discovery, neurocognitive/neurobehavioral and neurorehabilitation, and treatment approaches in the areas of TBI as well as other forms of TBI-induced disorders (CTE, AD, and PTE). We welcome original research or review papers that demonstrate the mechanisms of neuroprotection in clinical and experimental TBI in clinical settings. Submissions focusing on neuropathological molecular mechanisms involving proteomic, metabolomic, and imaging studies are encouraged.

Dr. Firas Kobeissy
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

traumatic brain injury
blood–brain barrier
neuroinflammation
glutamate toxicity
Alzheimer’s disease
Parkinson’s disease
chronic traumatic encephalopathy
neurocognitive
neurobehavioral
neurorehabilitation

Published Papers (4 papers)

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Research

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18 pages, 4181 KiB

Open AccessArticle

Therapeutic Efficiency of Proteins Secreted by Glial Progenitor Cells in a Rat Model of Traumatic Brain Injury

by Diana I. Salikhova, Victoria V. Golovicheva, Timur Kh. Fatkhudinov, Yulia A. Shevtsova, Anna G. Soboleva, Kirill V. Goryunov, Alexander S. Dyakonov, Victoria O. Mokroysova, Natalia S. Mingaleva, Margarita O. Shedenkova, Oleg V. Makhnach, Sergey I. Kutsev, Vladimir P. Chekhonin, Denis N. Silachev and Dmitry V. Goldshtein

Int. J. Mol. Sci. 2023, 24(15), 12341; https://doi.org/10.3390/ijms241512341 - 2 Aug 2023

Viewed by 1233

Abstract

Traumatic brain injuries account for 30–50% of all physical traumas and are the most common pathological diseases of the brain. Mechanical damage of brain tissue leads to the disruption of the blood–brain barrier and the massive death of neuronal, glial, and endothelial cells. These events trigger a neuroinflammatory response and neurodegenerative processes locally and in distant parts of the brain and promote cognitive impairment. Effective instruments to restore neural tissue in traumatic brain injury are lacking. Glial cells are the main auxiliary cells of the nervous system, supporting homeostasis and ensuring the protection of neurons through contact and paracrine mechanisms. The glial cells’ secretome may be considered as a means to support the regeneration of nervous tissue. Consequently, this study focused on the therapeutic efficiency of composite proteins with a molecular weight of 5–100 kDa secreted by glial progenitor cells in a rat model of traumatic brain injury. The characterization of proteins below 100 kDa secreted by glial progenitor cells was evaluated by proteomic analysis. Therapeutic effects were assessed by neurological outcomes, measurement of the damage volume by MRI, and an evaluation of the neurodegenerative, apoptotic, and inflammation markers in different areas of the brain. Intranasal infusions of the composite protein product facilitated the functional recovery of the experimental animals by decreasing the inflammation and apoptotic processes, preventing neurodegenerative processes by reducing the amounts of phosphorylated Tau isoforms Ser396 and Thr205. Consistently, our findings support the further consideration of glial secretomes for clinical use in TBI, notably in such aspects as dose-dependent effects and standardization. Full article

(This article belongs to the Special Issue Neuropathology and Cellular Mechanisms in Traumatic Brain Injury 2.0)

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14 pages, 1002 KiB

Open AccessArticle

Blast-Induced Neurotrauma Results in Spatially Distinct Gray Matter Alteration Alongside Hormonal Alteration: A Preliminary Investigation

by Sarah C. Hellewell, Douglas A. Granger and Ibolja Cernak

Int. J. Mol. Sci. 2023, 24(7), 6797; https://doi.org/10.3390/ijms24076797 - 5 Apr 2023

Cited by 3 | Viewed by 1764

Abstract

Blast-induced neurotrauma (BINT) frequently occurs during military training and deployment and has been linked to long-term neuropsychological and neurocognitive changes, and changes in brain structure. As military personnel experience frequent exposures to stress, BINT may negatively influence stress coping abilities. This study aimed to determine the effects of BINT on gray matter volume and hormonal alteration. Participants were Canadian Armed Forces personnel and veterans with a history of BINT (n = 12), and first responder controls (n = 8), recruited due to their characteristic occupational stress professions. Whole saliva was collected via passive drool on the morning of testing and analyzed for testosterone (pg/mL), cortisol (μg/dL), and testosterone/cortisol (T/C) ratio. Voxel-based morphometry was performed to compare gray matter (GM) volume, alongside measurement of cortical thickness and subcortical volumes. Saliva analyses revealed distinct alterations following BINT, with significantly elevated testosterone and T/C ratio. Widespread and largely symmetric loci of reduced GM were found specific to BINT, particularly in the temporal gyrus, precuneus, and thalamus. These findings suggest that BINT affects hypothalamic–pituitary–adrenal and –gonadal axis function, and causes anatomically-specific GM loss, which were not observed in a comparator group with similar occupational stressors. These findings support BINT as a unique injury with distinct structural and endocrine consequences. Full article

(This article belongs to the Special Issue Neuropathology and Cellular Mechanisms in Traumatic Brain Injury 2.0)

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16 pages, 5046 KiB

Open AccessArticle

The Integrity of the Blood–Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury

by Matthew Boyko, Benjamin F. Gruenbaum, Dmitry Frank, Dmitry Natanel, Shahar Negev, Abed N. Azab, Guy Barsky, Boris Knyazer, Ora Kofman and Alexander Zlotnik

Int. J. Mol. Sci. 2023, 24(6), 5897; https://doi.org/10.3390/ijms24065897 - 20 Mar 2023

Cited by 5 | Viewed by 1544

Abstract

A healthy blood–brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development. Full article

(This article belongs to the Special Issue Neuropathology and Cellular Mechanisms in Traumatic Brain Injury 2.0)

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Review

Jump to: Research

22 pages, 863 KiB

Open AccessReview

Fluid-Based Protein Biomarkers in Traumatic Brain Injury: The View from the Bedside

by Denes V. Agoston and Adel Helmy

Int. J. Mol. Sci. 2023, 24(22), 16267; https://doi.org/10.3390/ijms242216267 - 13 Nov 2023

Cited by 1 | Viewed by 1590

Abstract

There has been an explosion of research into biofluid (blood, cerebrospinal fluid, CSF)-based protein biomarkers in traumatic brain injury (TBI) over the past decade. The availability of very large datasets, such as CENTRE-TBI and TRACK-TBI, allows for correlation of blood- and CSF-based molecular (protein), radiological (structural) and clinical (physiological) marker data to adverse clinical outcomes. The quality of a given biomarker has often been framed in relation to the predictive power on the outcome quantified from the area under the Receiver Operating Characteristic (ROC) curve. However, this does not in itself provide clinical utility but reflects a statistical association in any given population between one or more variables and clinical outcome. It is not currently established how to incorporate and integrate biofluid-based biomarker data into patient management because there is no standardized role for such data in clinical decision making. We review the current status of biomarker research and discuss how we can integrate existing markers into current clinical practice and what additional biomarkers do we need to improve diagnoses and to guide therapy and to assess treatment efficacy. Furthermore, we argue for employing machine learning (ML) capabilities to integrate the protein biomarker data with other established, routinely used clinical diagnostic tools, to provide the clinician with actionable information to guide medical intervention. Full article

(This article belongs to the Special Issue Neuropathology and Cellular Mechanisms in Traumatic Brain Injury 2.0)

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