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Biomedicines
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Recent Advances in Traumatic Brain Injury Using Large Animal Models
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Recent Advances in Traumatic Brain Injury Using Large Animal Models

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 4973

Special Issue Editors

Prof. Dr. Susan Margulies

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Guest Editor
Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA
Interests: traumatic brain injury; ventilator-induced lung injury; concussion; large animal models; swine; biomarkers; biomechanics
Dr. Anna Oeur

E-Mail Website
Guest Editor
Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA
Interests: traumatic brain injury; sports concussion; biomechanics; EEG; swine; concussion; event-related potentials

Special Issue Information

Dear Colleagues,

Traumatic brain injury is a paramount global health concern and presents a substantial economic burden worldwide. Detecting mild traumatic brain injury (mTBI), which constitutes the majority of TBI cases, poses challenges as brain abnormalities are not easily detected using conventional diagnostic imaging, despite cognitive dysfunction and prolonged impairment. From a physiological perspective, acute primary brain injury is believed to stem from tissue deformation caused by the inertial movement of the brain following rapid head rotation. In order to comprehend the mechanisms and pathophysiology of mTBI, large animal models are a valuable tool for studying the biomechanics of TBI as neuroanatomical characteristics, such as white and grey matter distinctions in addition to well-circumscribed gyri and sulci, appropriate the effects of mechanical loading on the brain.

This Special Issue will serve to address a preclinical platform for developing and evaluating diagnostic as well as prognostic tools and interventions through the presentation of original research articles, reviews, and rapid short communication papers focusing on "Recent Advances in Traumatic Brain Injury Using Large Animal Models". The primary target audience for this Special Issue includes researchers employing an integrated biomechanics approach that incorporates large animal models, cell and tissue experiments, human studies, and the subsequent translation of these findings into preclinical therapeutic trials aimed at mitigating and preventing brain injuries.

Prof. Dr. Susan Margulies
Dr. Anna Oeur
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. Biomedicines 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 2600 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
  • large animal models
  • biomarkers
  • experimental
  • neurotrauma
  • neurological disorders
  • biomechanics

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Published Papers (3 papers)

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Research

17 pages, 3420 KiB  
Article
Transient Increases in Alpha Power Relative to Healthy Reference Ranges in Awake Piglets After Repeated Rapid Head Rotations
by Anna Oeur, William H. Torp and Susan S. Margulies
Biomedicines 2024, 12(11), 2460; https://doi.org/10.3390/biomedicines12112460 - 26 Oct 2024
Viewed by 843
Abstract
Background/Objectives: Sports-related concussions are a main cause of cognitive dysfunction and somatic complaints, particularly in youth. While the majority of concussion symptoms resolve within one week, cognitive effects may persist. In this study, we sought to study changes to cognition within this [...] Read more.
Background/Objectives: Sports-related concussions are a main cause of cognitive dysfunction and somatic complaints, particularly in youth. While the majority of concussion symptoms resolve within one week, cognitive effects may persist. In this study, we sought to study changes to cognition within this acute time frame. Methods: In this current study, we use an established swine model of traumatic brain injury (TBI) to study the effects of single and repeated head rotations on resting-state electroencephalography (rs-EEG) in awake piglets in the acute (within 7 days) time period after injury. We studied both healthy and experimental groups to (1) establish healthy reference ranges (RRs; N = 23) for one-minute rs-EEG in awake piglets, (2) compare the effects of single (N = 12) and repeated head rotations (N = 13) on rs-EEG, and (3) examine the acute time course (pre-injury and days 1, 4, and 7 post-injury) in animals administered single and repeated head rotations. EEG data were Fourier transformed, and total (1–30 Hz) and relative power in the alpha (8–12 Hz), beta (16.5–25 Hz), delta (1–4 Hz), and theta (4–7.5 Hz) bands were analyzed. Results: Total power and relative alpha, beta, delta, and theta power were consistent measures across days in healthy animals. We found a significant and transient increase in relative alpha power after repeated injury on day 1 in all regions and a rise above the healthy RR in the frontal and left temporal regions. Conclusions: Future studies will expand the study duration to investigate and inform clinical prognoses from acute measurements of rs-EEG. Full article
(This article belongs to the Special Issue Recent Advances in Traumatic Brain Injury Using Large Animal Models)
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13 pages, 1447 KiB  
Article
Approachability and Sensory Changes Following Mild Traumatic Brain Injury in Pigs
by Mark Pavlichenko, Radina L. Lilova, Amanda Logan-Wesley, Karen M. Gorse and Audrey D. Lafrenaye
Biomedicines 2024, 12(11), 2427; https://doi.org/10.3390/biomedicines12112427 - 23 Oct 2024
Viewed by 1078
Abstract
Background/Objectives: Traumatic brain injury (TBI) is a global healthcare concern affecting millions, with wide-ranging symptoms including sensory and behavioral changes that can persist long-term. Due to similarities with human brain cytoarchitecture and inflammation, minipig models are advantageous for translational TBI research. However, gaps [...] Read more.
Background/Objectives: Traumatic brain injury (TBI) is a global healthcare concern affecting millions, with wide-ranging symptoms including sensory and behavioral changes that can persist long-term. Due to similarities with human brain cytoarchitecture and inflammation, minipig models are advantageous for translational TBI research. However, gaps in knowledge exist regarding their behavioral and sensory sequelae following injury. Methods: Therefore, in this study, we assessed changes in approachability using a forced human approach task (FHAT) and mechanical nociception using the von Frey test in adult male and female Yucatan minipigs for up to one week following a sham or central fluid percussion injury (cFPI). Specifically, the FHAT assessed each animal’s response to a forced interaction with either a known or unknown experimenter. To evaluate changes in nociceptive sensory sensitivity, von Frey monofilaments ranging from 0.008 to 300 g of force were applied to the pinna of the ear or base of the tail. Results: We found that forced approachability was affected by experimenter familiarity as well as cFPI in a sex-specific manner at subacute timepoints. We also found reductions in sensitivity following cFPI on the ear in male minipigs and on the tail in female minipigs. Conclusion: Overall, the current study demonstrates that cFPI produces both behavioral and sensory changes in minipigs up to one-week post-injury. Full article
(This article belongs to the Special Issue Recent Advances in Traumatic Brain Injury Using Large Animal Models)
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21 pages, 7127 KiB  
Article
Human-Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Limits Tissue Damage and Promotes Tissue Regeneration and Functional Recovery in a Pediatric Piglet Traumatic-Brain-Injury Model
by Sarah L. Schantz, Sydney E. Sneed, Madison M. Fagan, Morgane E. Golan, Savannah R. Cheek, Holly A. Kinder, Kylee J. Duberstein, Erin E. Kaiser and Franklin D. West
Biomedicines 2024, 12(8), 1663; https://doi.org/10.3390/biomedicines12081663 - 25 Jul 2024
Viewed by 2571
Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability in pediatric patients and often results in delayed neural development and altered connectivity, leading to lifelong learning, memory, behavior, and motor function deficits. Induced pluripotent stem cell-derived neural stem cells (iNSCs) [...] Read more.
Traumatic brain injury (TBI) is a leading cause of death and disability in pediatric patients and often results in delayed neural development and altered connectivity, leading to lifelong learning, memory, behavior, and motor function deficits. Induced pluripotent stem cell-derived neural stem cells (iNSCs) may serve as a novel multimodal therapeutic as iNSCs possess neuroprotective, regenerative, and cell-replacement capabilities post-TBI. In this study, we evaluated the effects of iNSC treatment on cellular, tissue, and functional recovery in a translational controlled cortical impact TBI piglet model. Five days post-craniectomy (n = 6) or TBI (n = 18), iNSCs (n = 7) or PBS (n = 11) were injected into perilesional brain tissue. Modified Rankin Scale (mRS) neurological evaluation, magnetic resonance imaging, and immunohistochemistry were performed over the 12-week study period. At 12-weeks post-transplantation, iNSCs showed long-term engraftment and differentiation into neurons, astrocytes, and oligodendrocytes. iNSC treatment enhanced endogenous neuroprotective and regenerative activities indicated by decreasing intracerebral immune responses, preserving endogenous neurons, and increasing neuroblast formation. These cellular changes corresponded with decreased hemispheric atrophy, midline shift, and lesion volume as well as the preservation of cerebral blood flow. iNSC treatment increased piglet survival and decreased mRS scores. The results of this study in a predictive pediatric large-animal pig model demonstrate that iNSC treatment is a robust multimodal therapeutic that has significant promise in potentially treating human pediatric TBI patients. Full article
(This article belongs to the Special Issue Recent Advances in Traumatic Brain Injury Using Large Animal Models)
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