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Brain Sciences
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Frontiers in Biomarkers of Brain Injury
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Frontiers in Biomarkers of Brain Injury

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurorehabilitation".

Deadline for manuscript submissions: closed (5 December 2021) | Viewed by 17487

Special Issue Editor

Dr. Sergio Bagnato

E-Mail Website
Guest Editor
Unit of Neurophysiology and Unit for Severe Acquired Brain Injuries, Rehabilitation Department, Giuseppe Giglio Foundation, 90015 Cefalù, Italy
Interests: coma; disorders of consciousness; vegetative state; traumatic brain injury; biomarkers; clinical neurophysiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A biomarker of brain injury is any measurable indicator of central nervous system injury. Biomarkers in medicine are currently used for diagnosis, evaluation of disease severity, and prognosis. This Special Issue aims to collect papers about a broad range of pathological conditions, from acute brain injuries (e.g., traumatic brain injuries, hypoxic–ischemic brain injury, subarachnoid hemorrhage, ischemic stroke) to demyelinating diseases (e.g., multiple sclerosis) and neurodegenerative disease (e.g., Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease). We are especially interested in blood and cerebrospinal fluid biomarkers, but neurophysiological and neuroimaging studies will also be considered if they provide clear evidence of a marker of brain injury. Both studies on animal models and humans will be evaluated. Research and review papers will be welcomed.

Yours sincerely,

Dr. Sergio Bagnato
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. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). 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
  • hypoxic-ischemic brain injury
  • Alzheimer’s disease
  • spinal cord injury
  • cerebrospinal fluid biomarkers
  • blood biomarkers

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Published Papers (6 papers)

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Editorial

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2 pages, 183 KiB  
Editorial
Biomarkers of Brain Injury: A Window on Mechanisms of Injury and Recovery in the Brain
by Sergio Bagnato
Brain Sci. 2022, 12(3), 362; https://doi.org/10.3390/brainsci12030362 - 9 Mar 2022
Cited by 1 | Viewed by 1786
Abstract
The decision-making process regarding management after severe acute brain injury is based on clinical evaluation and depends on the injury etiology as well as radiological and neurophysiological data [...] Full article
(This article belongs to the Special Issue Frontiers in Biomarkers of Brain Injury)

Research

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10 pages, 652 KiB  
Article
Glycans as Potential Diagnostic Markers of Traumatic Brain Injury
by Mårten Kvist, Lasse Välimaa, Adrian Harel, Jussi P. Posti, Melissa Rahi, Ilkka Saarenpää, Mikko Visuri, Anna Östberg and Jaakko Rinne
Brain Sci. 2021, 11(11), 1480; https://doi.org/10.3390/brainsci11111480 - 9 Nov 2021
Cited by 4 | Viewed by 3697
Abstract
The diagnosis of mild traumatic brain injury (TBI) is challenging in the acute setting because the symptoms are nonspecific and often transient, or they develop with a delay. In these cases, the criteria for acute head imaging are frequently not fulfilled. This may [...] Read more.
The diagnosis of mild traumatic brain injury (TBI) is challenging in the acute setting because the symptoms are nonspecific and often transient, or they develop with a delay. In these cases, the criteria for acute head imaging are frequently not fulfilled. This may lead to missed diagnoses in emergency care. There is a need for developing a rapid diagnostic test to verify the presence of TBI using body fluids. Blood, urine, and saliva samples from 11 adult patients (mean age 64 years, SD 24 years) with acute and clinically diagnosed TBI, and 12 healthy volunteers were collected at Turku University Hospital during a period of 5 months. The injuries necessitated hospitalization for at least one day. The TBIs were classified mild in nine cases and severe in two cases. The mean period between the trauma and the time for obtaining the samples was 27 h, SD 11 h. The samples were analyzed in an ISO-certified laboratory for the number of lectin-bound glycan molecules indicating destruction of nerve tissue. The screening was performed on several possible glycans for binding, and the measurement by degree of fluorescence. In the analysis, the group of patients with TBI was compared with healthy volunteers. The results showed a significant decrease (p < 0.05, Wilcoxon rank–sum two-sided test) in the level of two glycans in plasma, but no significant increase for any glycan; in saliva, one glycan showed a significant increase in the TBI group; in urine, three glycans were significantly different between the groups (one showed an increase, whereas two showed a decrease). The results support the idea of conducting more research on how diagnostic glycans could be detected in body fluids after TBI. As a proof-of-concept, significant changes in the concentration of five glycans were found in plasma, saliva, and urine between TBI patients and healthy controls. This may enable the development of a rapid body fluid-based point-of-care test to identify patients with TBI after a head injury. Full article
(This article belongs to the Special Issue Frontiers in Biomarkers of Brain Injury)
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12 pages, 821 KiB  
Article
Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case—Control Longitudinal Study in Human Premature Neonates
by Dimitra Metallinou, Grigorios Karampas, Eleftheria Lazarou, Nikoletta Iacovidou, Panagiota Pervanidou, Katerina Lykeridou, George Mastorakos and Demetrios Rizos
Brain Sci. 2021, 11(9), 1243; https://doi.org/10.3390/brainsci11091243 - 20 Sep 2021
Cited by 4 | Viewed by 2082
Abstract
Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during [...] Read more.
Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI. Full article
(This article belongs to the Special Issue Frontiers in Biomarkers of Brain Injury)
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11 pages, 1145 KiB  
Article
Sustained Axonal Degeneration in Prolonged Disorders of Consciousness
by Sergio Bagnato, Maria Enza D’Ippolito, Cristina Boccagni, Antonio De Tanti, Lucia Francesca Lucca, Antonio Nardone, Pamela Salucci, Teresa Fiorilla, Valeria Pingue, Serena Gennaro, Maria Ursino, Valentina Colombo, Teresa Barone, Francesca Rubino and Maria Andriolo
Brain Sci. 2021, 11(8), 1068; https://doi.org/10.3390/brainsci11081068 - 14 Aug 2021
Cited by 8 | Viewed by 2477
Abstract
(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) [...] Read more.
(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL; both p < 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology. Full article
(This article belongs to the Special Issue Frontiers in Biomarkers of Brain Injury)
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Other

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7 pages, 881 KiB  
Case Report
Clinical Cognitive Motor Dissociation: A Case Report Showing How Pitfalls Can Hinder Early Clinical Detection of Awareness
by Jane Jöhr, Viviana Aureli, Ivo Meyer, Giulia Cossu and Karin Diserens
Brain Sci. 2022, 12(2), 157; https://doi.org/10.3390/brainsci12020157 - 25 Jan 2022
Cited by 3 | Viewed by 2685
Abstract
This study presents the case of a brain-injured patient whose pathological awakening after coma and absence of interaction led to a diagnosis of lack of consciousness when standard clinical scales were administered. However, we were able to demonstrate conscious perception in this patient [...] Read more.
This study presents the case of a brain-injured patient whose pathological awakening after coma and absence of interaction led to a diagnosis of lack of consciousness when standard clinical scales were administered. However, we were able to demonstrate conscious perception in this patient from initial clinical assessments using the Motor Behaviour Tool in the acute stage, complemented by a systematic search for potential obstacles blocking his execution of motor responses (pitfalls). This refinement of the diagnosis enabled prediction of a favourable outcome despite the severity of the lesions, with the patient’s evolution confirming our prediction. Faced with an unresponsive patient, every specialist should go beyond the absence of response with the standard scores, consider the possibility of a hidden consciousness and look for rigorous ways of proving it. Full article
(This article belongs to the Special Issue Frontiers in Biomarkers of Brain Injury)
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14 pages, 479 KiB  
Systematic Review
Correlation between Mild Traumatic Brain Injury-Induced Inflammatory Cytokines and Emotional Symptom Traits: A Systematic Review
by Shazia Malik, Omar Alnaji, Mahnoor Malik, Teresa Gambale and Michel Piers Rathbone
Brain Sci. 2022, 12(1), 102; https://doi.org/10.3390/brainsci12010102 - 12 Jan 2022
Cited by 12 | Viewed by 3784
Abstract
Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and [...] Read more.
Both mild traumatic brain injuries (mTBI) and systemic injuries trigger a transient neuroinflammatory response that result in similar clinical outcome. The ensuing physical, cognitive, and emotional symptoms fail to subside in approximately 15–20% of the concussed population. Emotional impairments, particularly depression, anxiety, and post-traumatic stress disorder (PTSD), are commonly associated with poor recovery following mTBI. These emotional impairments also have a significant neuroinflammatory component. We hypothesized that the inflammatory cytokines seen in mTBI patients with emotional symptoms would coincide with those commonly seen in patients with emotional symptoms without mTBI. A systematic review was conducted to identify the most common neuroinflammatory cytokines in the mTBI population with psychological symptoms (depression, anxiety, PTSD). The electronic databases EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and PSYCINFO were searched from data inception to 31 August 2021. A systematic screening approach was employed from screening to data analysis. A total of 994 articles were screened, 108 were selected for full article review, and 8 were selected for data analysis. The included studies consisted of 875 patients of which 81.3% were male. The mean sample size of patients with at least one mTBI was 73.8 ± 70.3 (range, 9–213), with a mean age of 33.9 ± 4.8 years. The most common cytokines associated with poor psychological outcomes involving PTSD and/or depression in the chronic mTBI population were IL-6, TNFα, IL-10, and CRP. Full article
(This article belongs to the Special Issue Frontiers in Biomarkers of Brain Injury)
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