Novel Method of Weighting Cumulative Helmet Impacts Improves Correlation with Brain White Matter Changes After One Football Season of Sub-concussive Head Blows

Merchant‐Borna, Kian; Asselin, Patrick D; Narayan, Darren A.; Abar, Beau; Jones, Courtney Marie Cora; Bazarian, Jeffrey J.

doi:10.1007/s10439-016-1680-9

Cited by 43 publications

(40 citation statements)

References 49 publications

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“…A number of neuroimaging studies have reported significant findings in WM changes based on DTI after only one season in athletes without concussions [Bazarian et al, ; Davenport et al, ; Koerte et al, ; Lao et al, ; Merchant‐Borna et al, ; Myer et al, ]. Our findings in Season 1 were based on a cohort of 10 athletes in the noncollar group and 13 athletes in the collar group, and replicated findings reported in our prior work in which larger cohorts (including the athletes in this study) were used in the analysis [Myer et al, ].…”

Section: Discussionsupporting

confidence: 86%

“…The effects of cumulative head impacts on young athletes over their entire careers are still unknown. Emerging neuroimaging investigations have generated evidence that suggests that the brain network may be affected, both structurally and functionally, during one season of contact sports, even with only nonclinical, subconcussive head impacts being tracked [Bahrami et al, ; Bazarian et al, ; Davenport et al, ; Lao et al, ; Koerte et al, ; Merchant‐Borna et al, ; Myer et al, ; Yuan et al, in press). When taken in aggregate over the career of the athlete, repetitive SCI could potentially increase the risk of season (or career) ending injuries, neurological impairments, and WM alterations [Bahrami et al, ; Myer et al, ].…”

Section: Introductionmentioning

confidence: 99%

“…Even in later adolescence, WM connectivity supporting executive control of behavior is still immature. Therefore, any compromise in WM integrity in youth or adolescence may have significant developmental implications [Asato et al, ; Bahrami et al, ; Davenport et al, ; Merchant‐Borna et al, ; Myer et al, ; Steinberg, ; ).…”

Section: Introductionmentioning

confidence: 99%

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White matter alterations over the course of two consecutive high‐school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study

Yuan

Foss

Thomas

et al. 2017

Human Brain Mapping

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The cumulative effects of repetitive subclinical head impacts during sports may result in chronic white matter (WM) changes and possibly, neurodegenerative sequelae. In this pilot study, we investigated the longitudinal WM changes over the course of two consecutive high-school football seasons and explored the long-term effects of a jugular vein compression collar on these WM alterations. Diffusion tensor imaging data were prospectively collected both pre-and postseason in the two consecutive seasons. Participants were assigned into either collar or noncollar groups. Tract-based spatial statistics (TBSS) approach and region of interest-based approach were used to quantify changes in WM diffusion properties. Despite comparable exposure to repetitive head impacts, significant reductions in mean, axial, and/or radial diffusivity were identified in Season 1 in multiple WM regions in the Additional Supporting Information may be found in the online version of this article. noncollar group but not in the collar group. After an 8-to 9-month long off-season, these changes observed in the noncollar group partially and significantly reversed but also remained significantly different from the baseline. In Season 2, trend level WM alterations in the noncollar group were found but located in spatially different regions than Season 1. Last, the WM integrity in the collar group remained unchanged throughout the four time points. In conclusion, we quantitatively assessed the WM structural changes and partial reversal over the course of two consecutive high-school football seasons. In addition, the mitigated WM alterations in athletes in the collar group might indicate potential effect of the collar in ameliorating the changes against repetitive head impacts. Hum Brain Mapp 39: 491-508, 2018.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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White matter alterations over the course of two consecutive high‐school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study

Yuan

Foss

Thomas

et al. 2017

Human Brain Mapping

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“…Furthermore, it is becoming clearer that multiple mild TBIs associate with a high risk of chronic traumatic encephalopathy (CTE), a dementia with distinctive clinical and pathologic features (Shively et al, 2012; Gardner and Yaffe, 2015). Additionally, there is evidence that sub-concussive head blows can induce acute brain changes as evaluated by imaging (Breedlove et al, 2012; Bazarian et al, 2014; Merchant-Borna et al, 2016), changes in neurochemistry (Lin et al, 2015) and cognitive function (McAllister et al, 2012), although the long-term consequences of these changes remain to be determined. Data from our gene array studies in rodents support a link between mild concussive and blast TBI and dementia as well as Parkinson’s disease, illustrated by the identification of gene sets and pathways associated with AD and Parkinson’s disease observed by Day 3 and 14 after injury (i.e., Blalock a1 Alzheimer’s disease incipient; Alzheimer’s disease dn and up and Parkin pathway (Tweedie et al, 2013a; Tweedie et al, 2016; Tweedie et al, 2013b).…”

Section: Discussionmentioning

confidence: 99%

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

Yang

Greig

Huang

et al. 2016

Neurobiology of Disease

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Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippocampus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-α oxygen analogue (PFT-α (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-α (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region’s role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-α or PFT-α (O) (2 mg/kg, i.v.) or vehicle at 5 h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24 h and 7 days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7 days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-α and, particularly, PFT-α (O) at 5 h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7 days after TBI, as evaluated by novel object recognition and open-field test. PFT-α and especially PFT-α (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-α (O), but not PFT-α, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-α (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-α (O) after TBI. Our data suggest that PFT-α and especially PFT-α (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties.

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“…Subconcussive impacts are defined as events similar to those giving rise to a concussion, or mild traumatic brain injury (mTBI), but apparently involving insufficient impact forces or accelerations to produce symptoms associated with mTBI (Shuttleworth-Edwards et al, 2008). Many contact sports, including American football, soccer, rugby, boxing, wrestling, and lacrosse, result in rather high numbers of repetitive head impacts throughout a season and career, with football having been observed to lead possibly to thousands of subconcussive impacts for a single player over the course of one season (Merchant-Borna et al, 2016, Talavage et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

The effect of repetitive subconcussive collisions on brain integrity in collegiate football players over a single football season: A multi-modal neuroimaging study

Slobounov

Walter

Breiter

et al. 2017

NeuroImage: Clinical

129

140

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The cumulative effect of repetitive subconcussive collisions on the structural and functional integrity of the brain remains largely unknown. Athletes in collision sports, like football, experience a large number of impacts across a single season of play. The majority of these impacts, however, are generally overlooked, and their long-term consequences remain poorly understood. This study sought to examine the effects of repetitive collisions across a single competitive season in NCAA Football Bowl Subdivision athletes using advanced neuroimaging approaches. Players were evaluated before and after the season using multiple MRI sequences, including T1-weighted imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), resting-state functional MRI (rs-fMRI), and susceptibility weighted imaging (SWI). While no significant differences were found between pre- and post-season for DTI metrics or cortical volumes, seed-based analysis of rs-fMRI revealed significant (p < 0.05) changes in functional connections to right isthmus of the cingulate cortex (ICC), left ICC, and left hippocampus. ASL data revealed significant (p < 0.05) increases in global cerebral blood flow (CBF), with a specific regional increase in right postcentral gyrus. SWI data revealed that 44% of the players exhibited outlier rates (p < 0.05) of regional decreases in SWI signal. Of key interest, athletes in whom changes in rs-fMRI, CBF and SWI were observed were more likely to have experienced high G impacts on a daily basis. These findings are indicative of potential pathophysiological changes in brain integrity arising from only a single season of participation in the NCAA Football Bowl Subdivision, even in the absence of clinical symptoms or a diagnosis of concussion. Whether these changes reflect compensatory adaptation to cumulative head impacts or more lasting alteration of brain integrity remains to be further explored.

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Novel Method of Weighting Cumulative Helmet Impacts Improves Correlation with Brain White Matter Changes After One Football Season of Sub-concussive Head Blows

Cited by 43 publications

References 49 publications

White matter alterations over the course of two consecutive high‐school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study

White matter alterations over the course of two consecutive high‐school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

The effect of repetitive subconcussive collisions on brain integrity in collegiate football players over a single football season: A multi-modal neuroimaging study

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