Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model

Mills, James D.; Bailes, Julian E.; Sedney, Cara L.; Hutchins, Heather; Sears, B.

doi:10.3171/2010.5.jns08914

Cited by 129 publications

(106 citation statements)

References 39 publications

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“…By modifying the Marmarou weight-drop model of concussion, we have been able to diminish impact forces to effect no obvious reaction or behavior change, and thus simulating less than a concussive injury. 2,[51][52][53] Using staining for amyloid precursor protein, we have shown that these subconcussive impacts reliably produce tearing of axons and the formation of axonal retraction bulbs in the brainstem-level descending motor pathways. In reducing the fall height of a 450-g mass from 2 to 1 m, we found no alteration of consciousness or responsiveness but significant numbers of amyloid precursor protein-positive axons compared with the number in controls (JD Mills, JE Bailes, unpublished data, 2010).…”

Section: Laboratory Evidence Of Subconcussive Effectsmentioning

confidence: 97%

Role of subconcussion in repetitive mild traumatic brain injury

Bailes

Petraglia

Omalu

et al. 2013

JNS

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463

340

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Research now suggests that head impacts commonly occur during contact sports in which visible signs or symptoms of neurological dysfunction may not develop despite those impacts having the potential for neurological injury. Recent biophysics studies utilizing helmet accelerometers have indicated that athletes at the collegiate and high school levels sustain a surprisingly high number of head impacts ranging from several hundred to well over 1000 during the course of a season. The associated cumulative impact burdens over the course of a career are equally important. Clinical studies have also identified athletes with no readily observable symptoms but who exhibit functional impairment as measured by neuropsychological testing and functional MRI. Such findings have been corroborated by diffusion tensor imaging studies demonstrating axonal injury in asymptomatic athletes at the end of a season. Recent autopsy data have shown that there are subsets of athletes in contact sports who do not have a history of known or identified concussions but nonetheless have neurodegenerative pathology consistent with chronic traumatic encephalopathy. Finally, emerging laboratory data have demonstrated significant axonal injury, blood-brain barrier permeability, and evidence of neuroinflammation, all in the absence of behavioral changes. Such data suggest that subconcussive level impacts can lead to significant neurological alterations, especially if the blows are repetitive. The authors propose “subconcussion” as a significant emerging concept requiring thorough consideration of the potential role it plays in accruing sufficient anatomical and/or physiological damage in athletes and military personnel, such that the effects of these injuries are clinically expressed either contemporaneously or later in life.

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Section: Laboratory Evidence Of Subconcussive Effectsmentioning

confidence: 97%

Role of subconcussion in repetitive mild traumatic brain injury

Bailes

Petraglia

Omalu

et al. 2013

JNS

Self Cite

463

340

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“…Docosahexaenoic acid (DHA), for example, is an omega-3 fatty acid that exhibits strong anti-inflammatory and neuroprotective effects 193 . In experimental models of TBI, DHA supplementation is known to reduce axonal damage in rodents 194 . This finding was recently supported in a clinical study of collegiate football players where prophylactic DHA supplementation significantly reduced serum levels of a known biomarker (Neurofilament Light; NFL) for axonal damage that was otherwise significantly elevated over the course of the season in athletes without DHA 195 .…”

Section: Nutritional Supplementationmentioning

confidence: 99%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

155

103

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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“…Several studies support the use of oxygen-radical scavengers, steroids, neurotrophic factors, or dietary supplementation, 183,[190][191][192][193][194] Although each of these classes of agents shows various degrees of axonal protection, they, too, will require further development. In addition, other promising agents are in the pipeline, including erythropoietin and somatostatin, and these, too, will require detailed evaluation.…”

Section: Additional Therapeutic Approachesmentioning

confidence: 99%

Therapy Development for Diffuse Axonal Injury

Smith

Hicks

Povlishock

2013

Journal of Neurotrauma

174

146

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Diffuse axonal injury (DAI) remains a prominent feature of human traumatic brain injury (TBI) and a major player in its subsequent morbidity. The importance of this widespread axonal damage has been confirmed by multiple approaches including routine postmortem neuropathology as well as advanced imaging, which is now capable of detecting the signatures of traumatically induced axonal injury across a spectrum of traumatically brain-injured persons. Despite the increased interest in DAI and its overall implications for brain-injured patients, many questions remain about this component of TBI and its potential therapeutic targeting. To address these deficiencies and to identify future directions needed to fill critical gaps in our understanding of this component of TBI, the National Institute of Neurological Disorders and Stroke hosted a workshop in May 2011. This workshop sought to determine what is known regarding the pathogenesis of DAI in animal models of injury as well as in the human clinical setting. The workshop also addressed new tools to aid in the identification of this axonal injury while also identifying more rational therapeutic targets linked to DAI for continued preclinical investigation and, ultimately, clinical translation. This report encapsulates the oral and written components of this workshop addressing key features regarding the pathobiology of DAI, the biomechanics implicated in its initiating pathology, and those experimental animal modeling considerations that bear relevance to the biomechanical features of human TBI. Parallel considerations of alternate forms of DAI detection including, but not limited to, advanced neuroimaging, electrophysiological, biomarker, and neurobehavioral evaluations are included, together with recommendations for how these technologies can be better used and integrated for a more comprehensive appreciation of the pathobiology of DAI and its overall structural and functional implications. Lastly, the document closes with a thorough review of the targets linked to the pathogenesis of DAI, while also presenting a detailed report of those target-based therapies that have been used, to date, with a consideration of their overall implications for future preclinical discovery and subsequent translation to the clinic. Although all participants realize that various research gaps remained in our understanding and treatment of this complex component of TBI, this workshop refines these issues providing, for the first time, a comprehensive appreciation of what has been done and what critical needs remain unfulfilled.

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Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model

Cited by 129 publications

References 39 publications

Role of subconcussion in repetitive mild traumatic brain injury

Role of subconcussion in repetitive mild traumatic brain injury

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Therapy Development for Diffuse Axonal Injury

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