References

2016

Steiger, B

Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion Journal Article

In: Physician Leadership Journal, vol. 3, no. 2, pp. 8–10, 2016.

Abstract | BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Football, Athletic Injuries/co [Complications], Brain Injury, Chronic, Chronic/et [Etiology], Humans, Motion Pictures as Topic

O'Kane, J W

Is Heading in Youth Soccer Dangerous Play? Journal Article

In: Physician & Sportsmedicine, vol. 44, no. 2, pp. 190–194, 2016.

Abstract | BibTeX | Tags: *Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention & Control], Brain Injuries/pc [Prevention & Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention & Control], Humans, Risk Factors, UNITED States

@article{OKane2016,

title = {Is Heading in Youth Soccer Dangerous Play?},

author = {O'Kane, J W},

year  = {2016},

date = {2016-01-01},

journal = {Physician \& Sportsmedicine},

volume = {44},

number = {2},

pages = {190--194},

abstract = {BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.},

keywords = {*Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention \&amp; Control], Brain Injuries/pc [Prevention \&amp; Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention \&amp; Control], Humans, Risk Factors, UNITED States},

pubstate = {published},

tppubtype = {article}

}

Mez, J; Solomon, T M; Daneshvar, D H; Stein, T D; McKee, A C

Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player Journal Article

In: JAMA Neurology, vol. 73, no. 3, pp. 353–355, 2016.

BibTeX | Tags: *Athletic Injuries/co [Complications], *Brain Injury, *Football, adult, Bacterial, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Endocarditis, Fatal Outcome, Heart Arrest, Humans, Male, Staphylococcal Infections

Underwood, E

NEUROSCIENCE. Can brain scans reveal concussion-linked disease? Journal Article

In: Science, vol. 352, no. 6288, pp. 881, 2016.

BibTeX | Tags: *Brain Concussion/co [Complications], *Brain Injury, *Neuroimaging/mt [Methods], *Positron-Emission Tomography/mt [Methods], *tau Proteins/an [Analysis], 0 (7-(6-fluoropyridin-3-yl)-5H-pyrido(4, 0 (Carbolines), 0 (tau Proteins), 3-b)indole, adult, Carbolines/pk [Pharmacokinetics], Chronic/di [Diagnosis], Chronic/et [Etiology], Humans

Lucke-Wold, B P; Turner, R C; Logsdon, A F; Nguyen, L; Bailes, J E; Lee, J M; Robson, M J; Omalu, B I; Huber, J D; Rosen, C L

Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy Journal Article

In: Journal of Neurosurgery, vol. 124, no. 3, pp. 687–702, 2016.

Abstract | BibTeX | Tags: *Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley

@article{Lucke-Wold2016,

title = {Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy},

author = {Lucke-Wold, B P and Turner, R C and Logsdon, A F and Nguyen, L and Bailes, J E and Lee, J M and Robson, M J and Omalu, B I and Huber, J D and Rosen, C L},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Neurosurgery},

volume = {124},

number = {3},

pages = {687--702},

abstract = {OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p \< 0.05), improved cognition (t = 6.532, p \< 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p \< 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.},

keywords = {*Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley},

pubstate = {published},

tppubtype = {article}

}

OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.

2015

Bieniek, K F; Ross, O A; Cormier, K A; Walton, R L; Soto-Ortolaza, A; Johnston, A E; DeSaro, P; Boylan, K B; Graff-Radford, N R; Wszolek, Z K; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W

Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article

In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.

Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks

@article{Bieniek2015,

title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},

author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},

year  = {2015},

date = {2015-01-01},

journal = {Acta Neuropathologica},

volume = {130},

number = {6},

pages = {877--889},

abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},

keywords = {*Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks},

pubstate = {published},

tppubtype = {article}

}

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.

Faden, A I; Loane, D J

Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Journal Article

In: Neurotherapeutics, vol. 12, no. 1, pp. 143–150, 2015.

Abstract | BibTeX | Tags: *Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]

@article{Faden2015,

title = {Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?},

author = {Faden, A I and Loane, D J},

year  = {2015},

date = {2015-01-01},

journal = {Neurotherapeutics},

volume = {12},

number = {1},

pages = {143--150},

abstract = {It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).},

keywords = {*Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]},

pubstate = {published},

tppubtype = {article}

}

Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A

Chronic traumatic encephalopathy and athletes Journal Article

In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.

Abstract | BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]

@article{Meehan3rd2015a,

title = {Chronic traumatic encephalopathy and athletes},

author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},

year  = {2015},

date = {2015-01-01},

journal = {Neurology},

volume = {85},

number = {17},

pages = {1504--1511},

abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},

keywords = {*Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]},

pubstate = {published},

tppubtype = {article}

}

Reference Search

Steiger, B

Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion Journal Article

In: Physician Leadership Journal, vol. 3, no. 2, pp. 8–10, 2016.

Abstract | BibTeX

O'Kane, J W

Is Heading in Youth Soccer Dangerous Play? Journal Article

In: Physician & Sportsmedicine, vol. 44, no. 2, pp. 190–194, 2016.

Abstract | BibTeX

@article{OKane2016,

title = {Is Heading in Youth Soccer Dangerous Play?},

author = {O'Kane, J W},

year  = {2016},

date = {2016-01-01},

journal = {Physician \& Sportsmedicine},

volume = {44},

number = {2},

pages = {190--194},

abstract = {BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Mez, J; Solomon, T M; Daneshvar, D H; Stein, T D; McKee, A C

Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player Journal Article

In: JAMA Neurology, vol. 73, no. 3, pp. 353–355, 2016.

BibTeX

Underwood, E

NEUROSCIENCE. Can brain scans reveal concussion-linked disease? Journal Article

In: Science, vol. 352, no. 6288, pp. 881, 2016.

BibTeX

Lucke-Wold, B P; Turner, R C; Logsdon, A F; Nguyen, L; Bailes, J E; Lee, J M; Robson, M J; Omalu, B I; Huber, J D; Rosen, C L

Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy Journal Article

In: Journal of Neurosurgery, vol. 124, no. 3, pp. 687–702, 2016.

Abstract | BibTeX

@article{Lucke-Wold2016,

title = {Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy},

author = {Lucke-Wold, B P and Turner, R C and Logsdon, A F and Nguyen, L and Bailes, J E and Lee, J M and Robson, M J and Omalu, B I and Huber, J D and Rosen, C L},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Neurosurgery},

volume = {124},

number = {3},

pages = {687--702},

abstract = {OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p \< 0.05), improved cognition (t = 6.532, p \< 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p \< 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Bieniek, K F; Ross, O A; Cormier, K A; Walton, R L; Soto-Ortolaza, A; Johnston, A E; DeSaro, P; Boylan, K B; Graff-Radford, N R; Wszolek, Z K; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W

Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article

In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.

Abstract | BibTeX

@article{Bieniek2015,

title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},

author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},

year  = {2015},

date = {2015-01-01},

journal = {Acta Neuropathologica},

volume = {130},

number = {6},

pages = {877--889},

abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Faden, A I; Loane, D J

Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Journal Article

In: Neurotherapeutics, vol. 12, no. 1, pp. 143–150, 2015.

Abstract | BibTeX

Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A

Chronic traumatic encephalopathy and athletes Journal Article

In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.

Abstract | BibTeX

@article{Meehan3rd2015a,

title = {Chronic traumatic encephalopathy and athletes},

author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},

year  = {2015},

date = {2015-01-01},

journal = {Neurology},

volume = {85},

number = {17},

pages = {1504--1511},

abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Most Referenced Keywords

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2016

Steiger, B

Meet Bennet Omalu, Md: The Physician Leader Whose Research Inspired the Movie Concussion Journal Article

In: Physician Leadership Journal, vol. 3, no. 2, pp. 8–10, 2016.

O'Kane, J W

Is Heading in Youth Soccer Dangerous Play? Journal Article

In: Physician & Sportsmedicine, vol. 44, no. 2, pp. 190–194, 2016.

@article{OKane2016,

title = {Is Heading in Youth Soccer Dangerous Play?},

author = {O'Kane, J W},

year  = {2016},

date = {2016-01-01},

journal = {Physician \& Sportsmedicine},

volume = {44},

number = {2},

pages = {190--194},

abstract = {BACKGROUND: Soccer is among the most popular youth sports with over 3 million youth players registered in the U.S. Soccer is unique in that players intentionally use their head to strike the ball, leading to concerns that heading could cause acute or chronic brain injury, especially in the immature brains of children. METHODS: Pub Med search without date restriction was conducted in November 2014 and August 2015 using the terms soccer and concussion, heading and concussion, and youth soccer and concussion. 310 articles were identified and reviewed for applicable content specifically relating to youth athletes, heading, and/or acute or chronic brain injury from soccer. RESULTS: Soccer is a low-risk sport for catastrophic head injury, but concussions are relatively common and heading often plays a role. At all levels of play, concussions are more likely to occur in the act of heading than with other facets of the game. While concussion from heading the ball without other contact to the head appears rare in adult players, some data suggests children are more susceptible to concussion from heading primarily in game situations. Contributing factors include biomechanical forces, less developed technique, and the immature brain's susceptibility to injury. CONCLUSIONS: There is no evidence that heading in youth soccer causes any permanent brain injury and there is limited evidence that heading in youth soccer can cause concussion. A reasonable approach based on U.S. Youth Soccer recommendations is to teach heading after age 10 in controlled settings, and heading in games should be delayed until skill acquisition and physical maturity allow the youth player to head correctly with confidence.},

keywords = {*Brain Injuries/et [Etiology], *Brain Injury, *Soccer/in [Injuries], Adolescent, Brain Concussion/et [Etiology], Brain Concussion/pc [Prevention \&amp; Control], Brain Injuries/pc [Prevention \&amp; Control], Brain Injury, Child, Chronic/et [Etiology], Chronic/pc [Prevention \&amp; Control], Humans, Risk Factors, UNITED States},

pubstate = {published},

tppubtype = {article}

}

Mez, J; Solomon, T M; Daneshvar, D H; Stein, T D; McKee, A C

Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player Journal Article

In: JAMA Neurology, vol. 73, no. 3, pp. 353–355, 2016.

Underwood, E

NEUROSCIENCE. Can brain scans reveal concussion-linked disease? Journal Article

In: Science, vol. 352, no. 6288, pp. 881, 2016.

Lucke-Wold, B P; Turner, R C; Logsdon, A F; Nguyen, L; Bailes, J E; Lee, J M; Robson, M J; Omalu, B I; Huber, J D; Rosen, C L

Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy Journal Article

In: Journal of Neurosurgery, vol. 124, no. 3, pp. 687–702, 2016.

@article{Lucke-Wold2016,

title = {Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy},

author = {Lucke-Wold, B P and Turner, R C and Logsdon, A F and Nguyen, L and Bailes, J E and Lee, J M and Robson, M J and Omalu, B I and Huber, J D and Rosen, C L},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Neurosurgery},

volume = {124},

number = {3},

pages = {687--702},

abstract = {OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p \< 0.05), improved cognition (t = 6.532, p \< 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p \< 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy.},

keywords = {*Blast Injuries/px [Psychology], *Brain Injury, *Endoplasmic Reticulum Stress/ph [Physiology], *Football/in [Injuries], *Wrestling/in [Injuries], adult, animal, Animals, Blast Injuries/et [Etiology], Blast Injuries/pa [Pathology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Disease Models, Humans, Male, Rats, Sprague-Dawley},

pubstate = {published},

tppubtype = {article}

}

2015

Bieniek, K F; Ross, O A; Cormier, K A; Walton, R L; Soto-Ortolaza, A; Johnston, A E; DeSaro, P; Boylan, K B; Graff-Radford, N R; Wszolek, Z K; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W

Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article

In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.

@article{Bieniek2015,

title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},

author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},

year  = {2015},

date = {2015-01-01},

journal = {Acta Neuropathologica},

volume = {130},

number = {6},

pages = {877--889},

abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},

keywords = {*Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks},

pubstate = {published},

tppubtype = {article}

}

Faden, A I; Loane, D J

Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Journal Article

In: Neurotherapeutics, vol. 12, no. 1, pp. 143–150, 2015.

@article{Faden2015,

title = {Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?},

author = {Faden, A I and Loane, D J},

year  = {2015},

date = {2015-01-01},

journal = {Neurotherapeutics},

volume = {12},

number = {1},

pages = {143--150},

abstract = {It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).},

keywords = {*Alzheimer Disease/et [Etiology], *Brain Injuries/co [Complications], *Brain Injury, *Encephalitis/et [Etiology], *Nerve Degeneration/et [Etiology], Alzheimer Disease/pa [Pathology], Animals, Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Encephalitis/pa [Pathology], Humans, Nerve Degeneration/pa [Pathology]},

pubstate = {published},

tppubtype = {article}

}

Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A

Chronic traumatic encephalopathy and athletes Journal Article

In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.

@article{Meehan3rd2015a,

title = {Chronic traumatic encephalopathy and athletes},

author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},

year  = {2015},

date = {2015-01-01},

journal = {Neurology},

volume = {85},

number = {17},

pages = {1504--1511},

abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},

keywords = {*Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]},

pubstate = {published},

tppubtype = {article}

}

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2016

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