The Influence of Systemic Immune Response and Sleep Modulation on the Secondary Effects of Traumatic Brain Injury in the Rodent Model

Sheeler, Carrie

doi:10.1523/jneurosci.1418-16.2016

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…This disparity could also point to long-term impacts of injury that are not restricted to TBI. Hospitalization, psychological trauma from the injury event, and biological responses associated with secondary injury (such as inflammation) could all contribute to alterations in brain structure and function even when the brain itself is not directly injured (McDonald et al , 2016;Sheeler, 2016;Yang et al , 2016;Nicholson et al , 2018;Ewing-Cobbs et al , 2019) .…”

Section: Discussionmentioning

confidence: 99%

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Dennis

Caeyenberghs

Hoskinson

et al. 2020

Preprint

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Annually, approximately 3 million children around the world experience traumatic brain injuries (TBIs), of which up to 20% are characterized as moderate to severe (msTBI) and/or have abnormal imaging findings. Affected children are vulnerable to long-term cognitive and behavioral dysfunction, as injury can disrupt or alter ongoing brain maturation. Post-injury outcomes are highly variable, and there is only limited understanding of how inter-individual differences in outcomes arise. Small sample sizes have also complicated efforts to better understand factors influencing the impact of TBI on the developing brain. White matter (WM) disruption is a critical aspect of TBI neuropathology and diffusion MRI (dMRI) is particularly sensitive to microstructural abnormalities. Here we present the results of a coordinated analysis of dMRI data across ten cohorts from three countries. We had three primary aims: (1) to characterize the nature and extent of WM disruption across key post-injury intervals (acute/subacute - within 2 months, post-acute - 2-6 months, chronic - 6+ months); (2) evaluate the impact of age and sex on WM in the context of injury; and (3) to examine associations between WM and neurobehavioral outcomes. Based on data from 507 children and adolescents (244 with complicated mild to severe TBI and 263 control children), we report widespread WM disruption across all post-injury intervals. As expected, injury severity was a significant contributor to the pattern and extent of WM degradation, but explained less variance in dMRI measures with increasing time since injury, supporting other research indicating that other factors contribute increasingly to outcomes over time. The corpus callosum appears to be particularly vulnerable to injury, an effect that persists years post-TBI. We also report sex differences in the effect of TBI on the uncinate fasciculus (UNC), a structure with a key role in emotion regulation. Females with a TBI had significantly lower fractional anisotropy (FA) in the UNC than those with no TBI, and this phenomenon was further associated with more frequent parent-reported behavioral problems as measured by the Child Behavior Checklist (CBCL). These effects were not detected in males. With future harmonization of imaging and neurocognitive data, more complex modeling of factors influencing outcomes will be possible and help to identify clinically-meaningful patient subtypes.

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Section: Discussionmentioning

confidence: 99%

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Dennis

Caeyenberghs

Hoskinson

et al. 2020

Preprint

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“…While these recent findings support similarities between children with mild TBI and OI, we still lack a complete understanding of the underlying neurobiological mechanisms accounting for these similarities and work is greatly needed in this area. Even in the absence of an orthopedic or extracranial injury, systemic trauma that is associated with a subsequent inflammatory response may alter blood brain barrier function and permeability, causing neuroinflammatory responses that might also result in structural and functional brain changes [McDonald et al, 2016;Nicholson et al, 2018;Sheeler, 2016;Yang et al, 2016]. With limited sample sizes, collecting both HC and OI controls has been beyond the capabilities of most studies to date.…”

Section: Pre-injury Variablesmentioning

confidence: 99%

Challenges and Opportunities for Neuroimaging in Young Patients with Traumatic Brain Injury: a Coordinated Effort towards Advancing Discovery from the ENIGMA Pediatric Moderate/Severe TBI Group

Tate¹,

Dennis²,

Caeyenberghs³

et al. 2019

Preprint

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Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population; however, research in this population lags behind research in adults. This may be due, in part, to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. Specific developmental issues also warrant attention in studies of children, and the ever-changing context of childhood and adolescence may require larger sample sizes than are commonly available to adequately address remaining questions related to TBI. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate-Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis. In this paper we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. We conclude with recommendations for future research in this field of study.

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Challenges and opportunities for neuroimaging in young patients with traumatic brain injury: a coordinated effort towards advancing discovery from the ENIGMA pediatric moderate/severe TBI group

Dennis

Caeyenberghs

Asarnow

et al. 2020

Brain Imaging and Behavior

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The Influence of Systemic Immune Response and Sleep Modulation on the Secondary Effects of Traumatic Brain Injury in the Rodent Model

Cited by 3 publications

References 16 publications

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric msTBI

Challenges and Opportunities for Neuroimaging in Young Patients with Traumatic Brain Injury: a Coordinated Effort towards Advancing Discovery from the ENIGMA Pediatric Moderate/Severe TBI Group

Challenges and opportunities for neuroimaging in young patients with traumatic brain injury: a coordinated effort towards advancing discovery from the ENIGMA pediatric moderate/severe TBI group

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