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Brain Sciences
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Prevention and Intervention for Pediatric Brain Injury
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Prevention and Intervention for Pediatric Brain Injury

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

Deadline for manuscript submissions: closed (1 January 2021) | Viewed by 18934

Special Issue Editor

Dr. Steven Threlkeld

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Guest Editor
Department of Neuroscience, Regis College, 235 Wellesley Street, Weston, MA 02493, USA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pediatric brain injury, ranging from the neonatal period to adolescence, represents a significant and heterogeneous medical problem. As observed in adulthood, developmental brain injury is marked by acute cellular toxicity and prolonged modifications in neuroimmunological signaling, resulting in brain tissue loss, age-dependent reorganization, and motor, cognitive, and other behavioral and psychiatric difficulties that can persist throughout life. Risk factors for pediatric brain injury very in prevalence based on age of acquisition, environmental context, and medical history. Injury occurring during the prolonged and dynamic process of brain assembly presents unique challenges for preclinical researchers and the development of clinical interventions. Despite challenges, in recent years both molecular and behavioral intervention approaches have shown promise for improving neuropathological and/or behavioral conditions linked to pediatric brain injury.

In this Special Issue, we seek original submissions of research or review articles from authors investigating a variety of prevention and/or intervention approaches from translational animal models or human clinical research. Submissions are encouraged from investigators studying immunological and other molecular therapeutics, those evaluating early behavioral intervention approaches, and/or researchers using neuroimaging and/or epidemiological approaches in clinical populations. Our aim is to assemble a Special Issue that incorporates diverse preclinical and clinical approaches in prevention and intervention for pediatric brain injury.

Dr. Steven Threlkeld
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

  • pediatric traumatic brain injury
  • neonatal hypoxia-ischemia
  • behavioral intervention
  • pharmacology
  • preventative care
  • immunotherapy
  • cellular therapy
  • cognitive intervention
  • sensory intervention
  • neuronal survival
  • neuronal plasticity

Published Papers (5 papers)

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Research

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12 pages, 448 KiB  
Article
Predictors of In-Hospital Mortality for School-Aged Children with Severe Traumatic Brain Injury
by Chih-Chi Chen, Carl P. C. Chen, Chien-Hung Chen, Yu-Wei Hsieh, Chia-Ying Chung and Chien-Hung Liao
Brain Sci. 2021, 11(2), 136; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11020136 - 21 Jan 2021
Cited by 4 | Viewed by 1913
Abstract
Traumatic brain injury (TBI) is the leading cause of mortality in children. There are few studies focused on school-aged children with TBI. We conducted this study to identify the early predictors of in-hospital mortality in school-aged children with severe TBI. In this 10 [...] Read more.
Traumatic brain injury (TBI) is the leading cause of mortality in children. There are few studies focused on school-aged children with TBI. We conducted this study to identify the early predictors of in-hospital mortality in school-aged children with severe TBI. In this 10 year observational cohort study, a total of 550 children aged 7–18 years with TBI were enrolled. Compared with mild/moderate TBI, children with severe TBI were older; more commonly had injury mechanisms of traffic accidents; and more neuroimage findings of subarachnoid hemorrhage (SAH), subdural hemorrhage (SDH), parenchymal hemorrhage, cerebral edema, and less epidural hemorrhage (EDH). The in-hospital mortality rate of children with severe TBI in our study was 23%. Multivariate analysis showed that falls, being struck by objects, motor component of Glasgow coma scale (mGCS), early coagulopathy, and SAH were independent predictors of in-hospital mortality. We concluded that school-aged children with severe TBI had a high mortality rate. Clinical characteristics including injury mechanisms of falls and being struck, a lower initial mGCS, early coagulopathy, and SAH are predictive of in-hospital mortality. Full article
(This article belongs to the Special Issue Prevention and Intervention for Pediatric Brain Injury)
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18 pages, 2225 KiB  
Article
Effects of Juvenile or Adolescent Working Memory Experience and Inter-Alpha Inhibitor Protein Treatment after Neonatal Hypoxia-Ischemia
by Aaron Bradford, Miranda Hernandez, Elaine Kearney, Luke Theriault, Yow-Pin Lim, Barbara S. Stonestreet and Steven W. Threlkeld
Brain Sci. 2020, 10(12), 999; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10120999 - 17 Dec 2020
Cited by 4 | Viewed by 1988
Abstract
Hypoxic-Ischemic (HI) brain injury in the neonate contributes to life-long cognitive impairment. Early diagnosis and therapeutic interventions are critical but limited. We previously reported in a rat model of HI two interventional approaches that improve cognitive and sensory function: administration of Inter-alpha Inhibitor [...] Read more.
Hypoxic-Ischemic (HI) brain injury in the neonate contributes to life-long cognitive impairment. Early diagnosis and therapeutic interventions are critical but limited. We previously reported in a rat model of HI two interventional approaches that improve cognitive and sensory function: administration of Inter-alpha Inhibitor Proteins (IAIPs) and early experience in an eight-arm radial water maze (RWM) task. Here, we expanded these studies to examine the combined effects of IAIPs and multiple weeks of RWM assessment beginning with juvenile or adolescent rats to evaluate optimal age windows for behavioral interventions. Subjects were divided into treatment groups; HI with vehicle, sham surgery with vehicle, and HI with IAIPs, and received either juvenile (P31 initiation) or adolescent (P52 initiation) RWM testing, followed by adult retesting. Error rates on the RWM decreased across weeks for all conditions. Whereas, HI injury impaired global performance as compared to shams. IAIP-treated HI subjects tested as juveniles made fewer errors as compared to their untreated HI counterparts. The juvenile group made significantly fewer errors on moderate demand trials and showed improved retention as compared to the adolescent group during the first week of adult retesting. Together, results support and extend our previous findings that combining behavioral and anti-inflammatory interventions in the presence of HI improves subsequent learning performance. Results further indicate sensitive periods for behavioral interventions to improve cognitive outcomes. Specifically, early life cognitive experience can improve long-term learning performance even in the presence of HI injury. Results from this study provide insight into typical brain development and the impact of developmentally targeted therapeutics and task-specific experience on subsequent cognitive processing. Full article
(This article belongs to the Special Issue Prevention and Intervention for Pediatric Brain Injury)
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16 pages, 3100 KiB  
Article
Ex Vivo MRI Analytical Methods and Brain Pathology in Preterm Lambs Treated with Postnatal Dexamethasone †
by Nathanael J. Yates, Kirk W. Feindel, Andrew Mehnert, Richard Beare, Sophia Quick, Dominique Blache, J. Jane Pillow and Rod W. Hunt
Brain Sci. 2020, 10(4), 211; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10040211 - 03 Apr 2020
Cited by 5 | Viewed by 3441
Abstract
Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological [...] Read more.
Postnatal glucocorticoids such as dexamethasone are effective in promoting lung development in preterm infants, but are prescribed cautiously due to concerns of neurological harm. We developed an analysis pipeline for post-mortem magnetic resonance imaging (MRI) to assess brain development and hence the neurological safety profile of postnatal dexamethasone in preterm lambs. Lambs were delivered via caesarean section at 129 days’ (d) gestation (full term ≈ 150 d) with saline-vehicle control (Saline, n = 9), low-dose tapered dexamethasone (cumulative dose = 0.75 mg/kg, n = 8), or high-dose tapered dexamethasone (cumulative dose = 2.67 mg/kg, n = 8), for seven days. Naïve fetal lambs (136 d gestation) were used as end-point maturation controls. The left-brain hemispheres were immersion-fixed in 10 % formalin (24 h), followed by paraformaldehyde (>6 months). Image sequences were empirically optimized for T1- and T2-weighted MRI and analysed using accessible methods. Spontaneous lesions detected in the white matter of the frontal cortex, temporo-parietal cortex, occipital lobe, and deep to the parahippocampal gyrus were confirmed with histology. Neither postnatal dexamethasone treatment nor gestation showed any associations with lesion incidence, frontal cortex (total, white, or grey matter) or hippocampal volume (all p > 0.05). Postnatal dexamethasone did not appear to adversely affect neurodevelopment. Our post-mortem MRI analysis pipeline is suitable for other animal models of brain development. Full article
(This article belongs to the Special Issue Prevention and Intervention for Pediatric Brain Injury)
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Review

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16 pages, 3877 KiB  
Review
Shaken Baby Syndrome: Magnetic Resonance Imaging Features in Abusive Head Trauma
by Gaia Cartocci, Vittorio Fineschi, Martina Padovano, Matteo Scopetti, Maria Camilla Rossi-Espagnet and Costanza Giannì
Brain Sci. 2021, 11(2), 179; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11020179 - 01 Feb 2021
Cited by 13 | Viewed by 8787
Abstract
In the context of child abuse spectrum, abusive head trauma (AHT) represents the leading cause of fatal head injuries in children less than 2 years of age. Immature brain is characterized by high water content, partially myelinated neurons, and prominent subarachnoid space, thus [...] Read more.
In the context of child abuse spectrum, abusive head trauma (AHT) represents the leading cause of fatal head injuries in children less than 2 years of age. Immature brain is characterized by high water content, partially myelinated neurons, and prominent subarachnoid space, thus being susceptible of devastating damage as consequence of acceleration–deceleration and rotational forces developed by violent shaking mechanism. Diagnosis of AHT is not straightforward and represents a medical, forensic, and social challenge, based on a multidisciplinary approach. Beside a detailed anamnesis, neuroimaging is essential to identify signs suggestive of AHT, often in absence of external detectable lesions. Magnetic resonance imaging (MRI) represents the radiation-free modality of choice to investigate the most typical findings in AHT, such as subdural hematoma, retinal hemorrhage, and hypoxic-ischemic damage and it also allows to detect more subtle signs as parenchymal lacerations, cranio-cervical junction, and spinal injuries. This paper is intended to review the main MRI findings of AHT in the central nervous system of infants, with a specific focus on both hemorrhagic and non-hemorrhagic injuries caused by the pathological mechanisms of shaking. Furthermore, this review provides a brief overview about the most appropriate and feasible MRI protocol to help neuroradiologists identifying AHT in clinical practice. Full article
(This article belongs to the Special Issue Prevention and Intervention for Pediatric Brain Injury)
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6 pages, 216 KiB  
Case Report
Pediatric Motor Inflammatory Neuropathy: The Role of Antiphospholipid Antibodies
by Claudia Brogna, Marco Luigetti, Giulia Norcia, Roberta Scalise, Gloria Ferrantini, Beatrice Berti, Domenico M. Romeo, Raffaele Manna, Eugenio Mercuri and Marika Pane
Brain Sci. 2020, 10(3), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10030156 - 07 Mar 2020
Viewed by 2168
Abstract
We report the clinical case of a nine-year-old girl who presented with progressive motor neuropathy, revealed via the detection of a higher delay in F-wave recording using digitalized nerve conduction/electromyography. Since the lupus anticoagulant (LAC) positivity, detected using diluted Russell viper venom time [...] Read more.
We report the clinical case of a nine-year-old girl who presented with progressive motor neuropathy, revealed via the detection of a higher delay in F-wave recording using digitalized nerve conduction/electromyography. Since the lupus anticoagulant (LAC) positivity, detected using diluted Russell viper venom time (dRVVT), switched to persistent serological anticardiolipin immunoglobulin G (IgG) positivity, a possible non-thrombotic antiphospholipid antibody (aPL)-related clinical manifestation was suspected, and intravenous immunoglobulin treatment (IVIG) was started. The IVIG treatment was well tolerated and the complete resolution of motor impairment was obtained after the third IVIG infusion. Our findings suggest that it could be useful to check for antiphospholipid antibodies in children with a rapid onset of progressive neurological signs in order to provide the beneficial use of IVIG in the treatment of pediatric aPL neurological conditions. Full article
(This article belongs to the Special Issue Prevention and Intervention for Pediatric Brain Injury)
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