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The Risks of Ignoring the Invisible Damages of Concussion: From Molecules to Pathology

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 July 2020) | Viewed by 14485

Special Issue Editors

Prof. Dr. Giuseppe Lazzarino

E-Mail Website
Guest Editor
Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95123 Catania, Italy
Interests: mitochondrial dysfunction; traumatic brain injury, oxidative/nitrosative stress; energy metabolism; neurodegenerations
Special Issues, Collections and Topics in MDPI journals
Dr. Valentina Di Pietro

E-Mail Website
Guest Editor
Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
Interests: TBI; animal models of TBI; microRNA
Dr. Stefano Signoretti

E-Mail
Guest Editor
Ospedale S. Eugenio, Rome, Italy

Special Issue Information

Dear Colleagues,

Concussion is a peculiar type of mild traumatic brain injury, frequently encountered in both contact (American football, boxing, martial arts, soccer, ice hockey) and noncontact (horse riding, alpine sky, car and moto races) sports. It occurs any time an external force, unnecessarily acting directly to the head, provokes rapid acceleration–deceleration of the brain. The consequences are evident at three levels: (i) clinical, with early and late symptoms spontaneously resolving (nearly in 100% of cases after the first concussion) in a relatively short time; (ii) neuropsychological, with cognitive deficits lasting slightly longer than neurological symptoms; and (iii) molecular, with an incredibly vast number of biochemical alterations of metabolic pathways and cycles, affecting cellular and subcellular functions, and lasting much longer than clinical symptoms and cognitive deficits. That is, concussion provokes silent and (almost) invisible changes of brain homeostasis, to date difficult to detect and monitor, causing a period of “vulnerability”, whose duration is scarcely predictable and during which the brain is exposed to catastrophic damages if a second concussion (second impact syndrome, SIS) should occur. Since concussive patients are negative on conventional neuroimaging techniques (CT scan, MRI) and symptoms rapidly clear off, concussion’s exact occurrence is largely underestimated, and sequelae of incomplete healing are dangerously under-concerned. Indeed, recurrent concussions may develop in progressive neurodegeneration, evolving into chronic traumatic encephalopathy (CTE).

The aim of this Special Issue is to receive original contributions or review articles on different aspects of concussion. Studies on concussion may be carried out either in animals or in humans and should be focused on highlighting new mechanisms negatively affecting cerebral cell functions, evidencing potential drug targets, determining new biomarkers which are useful to define healing and, in the case of athletes, their safe return to play, and reporting effective rehabilitation treatments. Ultimately, insights to better understand the molecular mechanisms triggering SIS or developing CTE would be highly esteemed.

Prof. Dr. Giuseppe Lazzarino
Dr. Valentina Di Pietro
Dr. Stefano Signoretti
Guest Editors

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

  • concussion
  • sports-related concussion
  • mitochondrial dysfunction
  • oxidative/nitrosative stress
  • neuroinflammation
  • brain energy metabolism
  • biomarkers of concussion
  • advanced neuroimaging techniques
  • post-concussive rehabilitation
  • SIS
  • CTE

Published Papers (4 papers)

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Research

12 pages, 246 KiB  
Article
The Relationship between Sport-Related Concussion and Sensation-Seeking
by Spencer W. Liebel, Kathryn L. Van Pelt, Gian-Gabriel P. Garcia, Lauren L. Czerniak, Michael A. McCrea, Thomas W. McAllister, Steven P. Broglio and on behalf of the CARE Consortium Investigators
Int. J. Mol. Sci. 2020, 21(23), 9097; https://doi.org/10.3390/ijms21239097 - 30 Nov 2020
Cited by 9 | Viewed by 2512
Abstract
Sensation-seeking, or the need for novel and exciting experiences, is thought to play a role in sport-related concussion (SRC), yet much remains unknown regarding these relationships and, more importantly, how sensation-seeking influences SRC risk. The current study assessed sensation-seeking, sport contact level, and [...] Read more.
Sensation-seeking, or the need for novel and exciting experiences, is thought to play a role in sport-related concussion (SRC), yet much remains unknown regarding these relationships and, more importantly, how sensation-seeking influences SRC risk. The current study assessed sensation-seeking, sport contact level, and SRC history and incidence in a large sample of NCAA collegiate athletes. Data included a full study sample of 22,374 baseline evaluations and a sub-sample of 2037 incident SRC. Independent samples t-test, analysis of covariance, and hierarchical logistic regression were constructed to address study hypotheses. Results showed that (1) among participants without SRC, sensation-seeking scores were higher in athletes playing contact sports compared to those playing limited- or non-contact sports (p < 0.001, R2 = 0.007, η2p = 0.003); (2) in the full study sample, a one-point increase in sensation-seeking scores resulted in a 21% greater risk of prior SRC (OR = 1.212; 95% CI: 1.154–1.272), and in the incident SRC sub-sample, a 28% greater risk of prior SRC (OR = 1.278; 95% CI: 1.104–1.480); (3) a one-point increase in sensation-seeking scores resulted in a 12% greater risk of incident SRC among the full study sample; and (4) sensation-seeking did not vary as a function of incident SRC (p = 0.281, η2p = 0.000). Our findings demonstrate the potential usefulness of considering sensation-seeking in SRC management. Full article
(This article belongs to the Special Issue The Risks of Ignoring the Invisible Damages of Concussion: From Molecules to Pathology)
16 pages, 1574 KiB  
Article
Saliva microRNA Biomarkers of Cumulative Concussion
by Steven D. Hicks, Robert P. Olympia, Cayce Onks, Raymond Y. Kim, Kevin J. Zhen, Gregory Fedorchak, Samantha DeVita, Aakanksha Rangnekar, Matthew Heller, Hallie Zwibel, Chuck Monteith, Zofia Gagnon, Callan D. McLoughlin, Jason Randall, Miguel Madeira, Thomas R. Campbell, Elise Fengler, Michael N. Dretsch, Christopher Neville and Frank A. Middleton
Int. J. Mol. Sci. 2020, 21(20), 7758; https://doi.org/10.3390/ijms21207758 - 20 Oct 2020
Cited by 14 | Viewed by 4726
Abstract
Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated [...] Read more.
Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects. Full article
(This article belongs to the Special Issue The Risks of Ignoring the Invisible Damages of Concussion: From Molecules to Pathology)
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19 pages, 3935 KiB  
Article
Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study
by Mario Forcione, Antonio Maria Chiarelli, David Perpetuini, David James Davies, Patrick O’Halloran, David Hacker, Arcangelo Merla and Antonio Belli
Int. J. Mol. Sci. 2020, 21(17), 6273; https://doi.org/10.3390/ijms21176273 - 29 Aug 2020
Cited by 1 | Viewed by 2863
Abstract
Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns [...] Read more.
Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed. Full article
(This article belongs to the Special Issue The Risks of Ignoring the Invisible Damages of Concussion: From Molecules to Pathology)
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14 pages, 2043 KiB  
Article
Differential Expression of Circulating Inflammatory Proteins Following Sport-Related Traumatic Brain Injury
by Ghazala Begum, Rahul Reddy, Kamal M. Yakoub, Antonio Belli, David J. Davies and Valentina Di Pietro
Int. J. Mol. Sci. 2020, 21(4), 1216; https://doi.org/10.3390/ijms21041216 - 12 Feb 2020
Cited by 12 | Viewed by 3692
Abstract
Sport-related traumatic brain injury (TBI) elicits a multifaceted inflammatory response leading to brain injury and morbidity. This response could be a predictive tool for the progression of TBI and to stratify the injury of which mild TBI is most prevalent. Therefore, we examined [...] Read more.
Sport-related traumatic brain injury (TBI) elicits a multifaceted inflammatory response leading to brain injury and morbidity. This response could be a predictive tool for the progression of TBI and to stratify the injury of which mild TBI is most prevalent. Therefore, we examined the differential expression of serum inflammatory markers overtime and identified novel markers in repetitively concussed athletes. Neuropsychological assessment by Wechsler Adult Intelligence Scale (WAIS) and Immediate Post Concussion Assessment and Cognitive Test (ImPACT) was performed on rugby players and serum was taken from healthy, concussed and repetitively concussed athletes. Serum was also obtained <1 week and >1 week after trauma and analyzed for 92 inflammatory protein markers. Fibroblast growth factor 21 (FGF21) and interleukin-7 (IL-7) differentiated repetitively concussed athletes. Macrophage chemotactic protein-1 (MCP-1), tumor necrosis factor superfamily member 14 (TNFSF14) were significantly reduced >1 week and chemokine (C-X3-C motif) ligand 1 (CX3CL1) upregulated <1 week after injury. FGF21 and MCP-1 negatively correlated with symptoms and their severity. We have identified dynamic changes in the inflammatory response overtime and in different classes of concussion correlating with disease progression. This data supports the use of inflammatory biomarkers as predictors of symptom development due to secondary complications of sport-related mTBI. Full article
(This article belongs to the Special Issue The Risks of Ignoring the Invisible Damages of Concussion: From Molecules to Pathology)
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