Neurotrauma: Mechanisms, Pathways, and Emerging Therapeutic Interventions

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 12648

Special Issue Editors


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Guest Editor
Department of Radiology, University of Florida, Gainesville, FL, USA
Interests: neurotrauma; radiology; neuroscience; neurointervention

Special Issue Information

Dear Colleagues,

Neurotrauma encompasses traumatic brain and spinal cord injuries. Its pathophysiological mechanisms, particularly primary injuries followed by secondary cascades like inflammation, oxidative stress, and excitotoxicity, merit further elucidation and serve as treatment targets. This Special Issue of Biomedicines focuses on the molecular and cellular pathways associated with neurotrauma. We aim to address advancements in diagnostic biomarkers, the utility of advanced imaging techniques, and the current and emerging treatments for neuroprotection and regeneration. We invite submissions of original research, reviews, and comprehensive studies that provide insights into these important areas.

The scope of this Special Issue includes but is not limited to:

  • Primary and secondary injury mechanisms in neurotrauma;
  • Molecular and cellular pathways in neurotrauma;
  • Role of inflammation post-neurotrauma;
  • Identification of new diagnostic biomarkers;
  • Utility of advanced imaging techniques in neurotrauma;
  • Therapeutic strategies focusing on neuroprotection and regeneration;
  • Reviews on current and emerging trends in neurotrauma research.

Dr. Kevin Pierre
Dr. Brandon Lucke-Wold
Guest Editors

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Keywords

  • neurotrauma
  • traumatic brain injury
  • spinal cord injury
  • inflammation
  • oxidative stress
  • excitotoxicity
  • diagnostic biomarkers
  • imaging techniques
  • neuroprotection
  • neuroregeneration

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Published Papers (7 papers)

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Research

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16 pages, 2889 KiB  
Article
Brachial Plexus Injury Influences Efferent Transmission on More than Just the Symptomatic Side, as Verified with Clinical Neurophysiology Methods Using Magnetic and Electrical Stimulation
by Agnieszka Wiertel-Krawczuk, Agnieszka Szymankiewicz-Szukała and Juliusz Huber
Biomedicines 2024, 12(7), 1401; https://doi.org/10.3390/biomedicines12071401 - 24 Jun 2024
Cited by 1 | Viewed by 1085
Abstract
The variety of sources of brachial plexus injuries (BPIs) and the severity and similarity of their clinical symptoms with those of other injuries make their differential diagnosis difficult. Enriching their diagnosis with objective high-sensitivity diagnostics such as clinical neurophysiology may lead to satisfactory [...] Read more.
The variety of sources of brachial plexus injuries (BPIs) and the severity and similarity of their clinical symptoms with those of other injuries make their differential diagnosis difficult. Enriching their diagnosis with objective high-sensitivity diagnostics such as clinical neurophysiology may lead to satisfactory treatment results, and magnetic stimulation (MEP) might be an advantageous addition to the diagnostic standard of electrical stimulation used in electroneurography (ENG). The asymptomatic side in BPI cases sometimes shows only subclinical neurological deficits; this study aimed to clarify the validity and utility of using MEP vs. ENG to detect neural conduction abnormalities. Twenty patients with a BPI and twenty healthy volunteers with matching demographic and anthropometric characteristics were stimulated at their Erb’s point in order to record the potentials evoked using magnetic and electrical stimuli to evaluate their peripheral motor neural transmission in their axillar, musculocutaneous, radial, and ulnar nerves. MEP was also used to verify the neural transmission in participants’ cervical roots following transvertebral stimulations, checking the compatibility and repeatability of the evoked potential recordings. The clinical assessment resulted in an average muscle strength of 3–1 (with a mean of 2.2), analgesia that mainly manifested in the C5–C7 spinal dermatomes, and a pain evaluation of 6–4 (mean of 5.4) on the symptomatic side using the Visual Analog Scale, with no pathological symptoms on the contralateral side. A comparison of the recorded potentials evoked with magnetic versus electrical stimuli revealed that the MEP amplitudes were usually higher, at p = 0.04–0.03, in most of the healthy volunteers’ recorded muscles than in those of the group of BPI patients, whose recordings showed that their CMAP and MEP amplitude values were lower on their more symptomatic than asymptomatic sides, at p = 0.04–0.009. In recordings following musculocutaneous and radial nerve electrical stimulation and ulnar nerve magnetic stimulation at Erb’s point, the values of the latencies were also longer on the patient’s asymptomatic side compared to those in the control group. The above outcomes prove the mixed axonal and demyelination natures of brachial plexus injuries. They indicate that different types of traumatic BPIs also involve the clinically asymptomatic side. Cases with predominantly median nerve lesions were detected in sensory nerve conduction studies (SNCSs). In 16 patients, electromyography revealed neurogenic damage to the deltoid and biceps muscles, with an active denervation process at work. The predominance of C5 and C6 brachial plexus injuries in the cervical root and upper/middle trunk of patients with BPI has been confirmed. A probable explanation for the bilateral symptoms of dysfunction detected via clinical neurophysiology methods in the examined BPI patients, who showed primarily unilateral damage, maybe the reaction of their internal neural spinal center’s organization. Even when subclinical, this may explain the poor BPI treatment outcomes that sometimes occur following long-term physical therapy or surgical treatment. Full article
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Review

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19 pages, 1540 KiB  
Review
The Relevance and Implications of Monoclonal Antibody Therapies on Traumatic Brain Injury Pathologies
by Ping Wang, Starlyn Okada-Rising, Anke H. Scultetus and Zachary S. Bailey
Biomedicines 2024, 12(12), 2698; https://doi.org/10.3390/biomedicines12122698 - 26 Nov 2024
Viewed by 543
Abstract
Traumatic brain injury (TBI) is a global public health concern. It remains one of the leading causes of morbidity and mortality. TBI pathology involves complex secondary injury cascades that are associated with cellular and molecular dysfunction, including oxidative stress, coagulopathy, neuroinflammation, neurodegeneration, neurotoxicity, [...] Read more.
Traumatic brain injury (TBI) is a global public health concern. It remains one of the leading causes of morbidity and mortality. TBI pathology involves complex secondary injury cascades that are associated with cellular and molecular dysfunction, including oxidative stress, coagulopathy, neuroinflammation, neurodegeneration, neurotoxicity, and blood–brain barrier (BBB) dysfunction, among others. These pathological processes manifest as a diverse array of clinical impairments. They serve as targets for potential therapeutic intervention not only in TBI but also in other diseases. Monoclonal antibodies (mAbs) have been used as key therapeutic agents targeting these mechanisms for the treatment of diverse diseases, including neurological diseases such as Alzheimer’s disease (AD). MAb therapies provide a tool to block disease pathways with target specificity that may be capable of mitigating the secondary injury cascades following TBI. This article reviews the pathophysiology of TBI and the molecular mechanisms of action of mAbs that target these shared pathological pathways in a wide range of diseases. Publicly available databases for various applications of mAb therapy were searched and further classified to assess relevance to TBI pathology and evaluate current stages of development. The authors intend for this review to highlight the potential impact of current mAb technology within pathological TBI processes. Full article
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24 pages, 1942 KiB  
Review
Potential Applications and Ethical Considerations for Artificial Intelligence in Traumatic Brain Injury Management
by Kryshawna Beard, Ashley M. Pennington, Amina K. Gauff, Kelsey Mitchell, Johanna Smith and Donald W. Marion
Biomedicines 2024, 12(11), 2459; https://doi.org/10.3390/biomedicines12112459 - 26 Oct 2024
Viewed by 1275
Abstract
Artificial intelligence (AI) systems have emerged as promising tools for rapidly identifying patterns in large amounts of healthcare data to help guide clinical decision making, as well as to assist with medical education and the planning of research studies. Accumulating evidence suggests AI [...] Read more.
Artificial intelligence (AI) systems have emerged as promising tools for rapidly identifying patterns in large amounts of healthcare data to help guide clinical decision making, as well as to assist with medical education and the planning of research studies. Accumulating evidence suggests AI techniques may be particularly useful for aiding the diagnosis and clinical management of traumatic brain injury (TBI)—a considerably heterogeneous neurologic condition that can be challenging to detect and treat. However, important methodological and ethical concerns with the use of AI in medicine necessitate close monitoring and regulation of these techniques as advancements continue. The purpose of this narrative review is to provide an overview of common AI techniques in medical research and describe recent studies on the possible clinical applications of AI in the context of TBI. Finally, the review describes the ethical challenges with the use of AI in medicine, as well as guidelines from the White House, the Department of Defense (DOD), the National Academies of Sciences, Engineering, and Medicine (NASEM), and other organizations on the appropriate uses of AI in research. Full article
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17 pages, 1410 KiB  
Review
Mesenchymal Stem Cell-Derived Exosomes as a Neuroregeneration Treatment for Alzheimer’s Disease
by Siddharth Shah, Hadeel M. Mansour, Tania M. Aguilar and Brandon Lucke-Wold
Biomedicines 2024, 12(9), 2113; https://doi.org/10.3390/biomedicines12092113 - 17 Sep 2024
Viewed by 1915
Abstract
Background: Alzheimer’s disease (AD) is the most prevalent kind of dementia and is a long-term degenerative disease. Pathologically, it is defined by the development of extracellular amyloid-β plaques and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. This causes neuronal death, particularly [...] Read more.
Background: Alzheimer’s disease (AD) is the most prevalent kind of dementia and is a long-term degenerative disease. Pathologically, it is defined by the development of extracellular amyloid-β plaques and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. This causes neuronal death, particularly in the hippocampus and cortex. Mesenchymal stem cell (MSC)-derived exosomes have been identified as possibly therapeutic and have promise for Alzheimer’s disease due to their regenerative characteristics. Methods: A systematic retrieval of information was performed on PubMed. A total of 60 articles were found in a search on mesenchymal stem cells, exosomes, and Alzheimer’s disease. A total of 16 ongoing clinical trials were searched and added from clinicaltrials.gov. We added 23 supporting articles to help provide information for certain sections. In total, we included 99 articles in this manuscript: 50 are review articles, 13 are preclinical studies, 16 are clinical studies, 16 are ongoing clinical trials, and 4 are observational studies. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on mesenchymal stem cell exosomes for Alzheimer’s disease were searched on clinicaltrials.gov. Results: Several experimental investigations have shown that MSC-Exo improves cognitive impairment in rats. In this review paper, we summarized existing understanding regarding the molecular and cellular pathways behind MSC-Exo-based cognitive function restoration, with a focus on MSC-Exo’s therapeutic potential in the treatment of Alzheimer’s disease. Conclusion: AD is a significant health issue in our culture and is linked to several important neuropathological characteristics. Exosomes generated from stem cells, such as mesenchymal stem cells (MSCs) or neural stem cells (NSCs), have been examined more and more in a variety of AD models, indicating that they may be viable therapeutic agents for the treatment of diverse disorders. Exosome yields may be increased, and their therapeutic efficacy can be improved using a range of tailored techniques and culture conditions. It is necessary to provide standardized guidelines for exosome manufacture to carry out excellent preclinical and clinical research. Full article
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14 pages, 893 KiB  
Review
Selective COX-2 Inhibitors as Neuroprotective Agents in Traumatic Brain Injury
by Matthew I. Hiskens, Anthony G. Schneiders and Andrew S. Fenning
Biomedicines 2024, 12(8), 1930; https://doi.org/10.3390/biomedicines12081930 - 22 Aug 2024
Viewed by 1152
Abstract
Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 [...] Read more.
Traumatic brain injury (TBI) is a significant contributor to mortality and morbidity in people, both young and old. There are currently no approved therapeutic interventions for TBI. Following TBI, cyclooxygenase (COX) enzymes generate prostaglandins and reactive oxygen species that perpetuate inflammation, with COX-1 and COX-2 isoforms providing differing responses. Selective COX-2 inhibitors have shown potential as neuroprotective agents. Results from animal models of TBI suggest potential treatment through the alleviation of secondary injury mechanisms involving neuroinflammation and neuronal cell death. Additionally, early clinical trials have shown that the use of celecoxib improves patient mortality and outcomes. This review aims to summarize the therapeutic effects of COX-2 inhibitors observed in TBI animal models, highlighting pertinent studies elucidating molecular pathways and expounding upon their mechanistic actions. We then investigated the current state of evidence for the utilization of COX-2 inhibitors for TBI patients. Full article
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34 pages, 7340 KiB  
Review
Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord
by Andrew R. Stevens, Antonio Belli and Zubair Ahmed
Biomedicines 2024, 12(3), 643; https://doi.org/10.3390/biomedicines12030643 - 13 Mar 2024
Cited by 2 | Viewed by 3172
Abstract
Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations and often causes profound and irreversible disability. Pathophysiological responses to trauma exacerbate the damage of an index injury, propagating the loss of function that the central nervous system [...] Read more.
Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations and often causes profound and irreversible disability. Pathophysiological responses to trauma exacerbate the damage of an index injury, propagating the loss of function that the central nervous system (CNS) cannot repair after the initial event is resolved. The way in which function is lost after injury is the consequence of a complex array of mechanisms that continue in the chronic phase post-injury to prevent effective neural repair. This review summarises the events after traumatic brain injury (TBI) and spinal cord injury (SCI), comprising a description of current clinical management strategies, a summary of known cellular and molecular mechanisms of secondary damage and their role in the prevention of repair. A discussion of current and emerging approaches to promote neuroregeneration after CNS injury is presented. The barriers to promoting repair after neurotrauma are across pathways and cell types and occur on a molecular and system level. This presents a challenge to traditional molecular pharmacological approaches to targeting single molecular pathways. It is suggested that novel approaches targeting multiple mechanisms or using combinatorial therapies may yield the sought-after recovery for future patients. Full article
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21 pages, 1844 KiB  
Review
Navigating the Complexities of Traumatic Encephalopathy Syndrome (TES): Current State and Future Challenges
by Arman Fesharaki-Zadeh
Biomedicines 2023, 11(12), 3158; https://doi.org/10.3390/biomedicines11123158 - 27 Nov 2023
Cited by 2 | Viewed by 2530
Abstract
Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES), were proposed to improve the [...] Read more.
Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES), were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer’s disease and CTE. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures. Full article
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