Ojo, J O; Mouzon, B C; Crawford, F
Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men Journal Article
In: Experimental Neurology, vol. 275, pp. 389–404, 2016.
Abstract | Links | BibTeX | Tags: amyloid beta protein, animal, Animal models, Animals, Astroglial tangles, Brain Injury, cell activation, Chronic, complication, Concussion, Craniocerebral Trauma, CTE, diffuse axonal injury, disease duration, disease model, Disease Models, genetic predisposition, gliosis, head injury, hippocampus, human, Humans, lifestyle modification, lithium, metabolism, Mice, microglia, minocycline, mouse, nervous system inflammation, Neurobehaviour, Neurofibrillary tangles, neuropathology, nonhuman, pathogenesis, pathology, priority journal, procedures, protein aggregation, protein analysis, protein blood level, protein cleavage, Repetitive TBI, Review, sex difference, stress activated protein kinase inhibitor, Systematic Review, Tau, tau protein, tau Proteins, Transgenic mice, Translational Medical Research, translational research, traumatic brain injury, trends
@article{Ojo2016,
title = {Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men},
author = {Ojo, J O and Mouzon, B C and Crawford, F},
doi = {10.1016/j.expneurol.2015.06.003},
year = {2016},
date = {2016-01-01},
journal = {Experimental Neurology},
volume = {275},
pages = {389--404},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been recognized as one of the major risk factors associated with CTE. Although these human studies have been informative, their retrospective design carries certain inherent limitations that should be cautiously interpreted. In particular, the current overriding issue in the CTE literature remains confusing in regard to appropriate definitions of terminology, variability in individual pathologies and the potential case selection bias in autopsy based studies. There are currently no epidemiological or prospective studies on CTE. Controlled preclinical studies in animals therefore provide an alternative means for specifically interrogating aspects of CTE pathogenesis. In this article, we review the current literature and discuss difficulties and challenges of developing in-vivo TBI experimental paradigms to explore the link between repetitive head trauma and tau-dependent changes. We provide our current opinion list of recommended features to consider for successfully modeling CTE in animals to better understand the pathobiology and develop therapeutics and diagnostics, and critical factors, which might influence outcome. We finally discuss the possible directions of future experimental research in the repetitive TBI/CTE field. © 2015 Elsevier Inc..},
keywords = {amyloid beta protein, animal, Animal models, Animals, Astroglial tangles, Brain Injury, cell activation, Chronic, complication, Concussion, Craniocerebral Trauma, CTE, diffuse axonal injury, disease duration, disease model, Disease Models, genetic predisposition, gliosis, head injury, hippocampus, human, Humans, lifestyle modification, lithium, metabolism, Mice, microglia, minocycline, mouse, nervous system inflammation, Neurobehaviour, Neurofibrillary tangles, neuropathology, nonhuman, pathogenesis, pathology, priority journal, procedures, protein aggregation, protein analysis, protein blood level, protein cleavage, Repetitive TBI, Review, sex difference, stress activated protein kinase inhibitor, Systematic Review, Tau, tau protein, tau Proteins, Transgenic mice, Translational Medical Research, translational research, traumatic brain injury, trends},
pubstate = {published},
tppubtype = {article}
}
Sikoglu, E M; Liso Navarro, A A; Czerniak, S M; McCafferty, J; Eisenstock, J; Stevenson, J H; King, J A; Moore, C M
Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study Journal Article
In: Cognitive and Behavioral Neurology, vol. 28, no. 4, pp. 181–187, 2015.
Abstract | Links | BibTeX | Tags: Adolescent, adult, Article, athlete, Athletic Injuries, biochemical analysis, bioenergy, brain concussion, clinical article, cognition, college, Concussion, energy consumption, Energy Metabolism, Female, high energy phosphate, human, Humans, Longitudinal studies, longitudinal study, Magnetic Resonance Spectroscopy, Male, metabolism, MR spectroscopy (phosphorus-31), neuroimaging, NTP, NUCLEAR magnetic resonance spectroscopy, nucleoside, nucleoside triphosphate, Nucleosides, Pathophysiology, phosphate, Phosphates, phosphorus, Phosphorus Isotopes, phosphorus nuclear magnetic resonance, PHYSIOLOGY, Prefrontal Cortex, priority journal, procedures, sport injury, Universities, university, Young Adult
@article{Sikoglu2015,
title = {Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study},
author = {Sikoglu, E M and {Liso Navarro}, A A and Czerniak, S M and McCafferty, J and Eisenstock, J and Stevenson, J H and King, J A and Moore, C M},
doi = {10.1097/WNN.0000000000000076},
year = {2015},
date = {2015-01-01},
journal = {Cognitive and Behavioral Neurology},
volume = {28},
number = {4},
pages = {181--187},
abstract = {Background: Although clinical evaluations and neurocognitive assessments are commonly used to evaluate the extent of and recovery from concussion, brain bioenergetics could provide a more quantitative marker. The neurometabolic response to a concussion is thought to increase neuronal energy consumption and thus the demand for nucleoside triphosphate (NTP). Objective: We investigated the possible disruption in high-energy metabolism within the prefrontal cortex of college athletes who had either had a concussion within the past 6 months (n=14) or had never had a concussion (n=13). We hypothesized that concussed athletes would have imbalanced brain bioenergetics resulting from increased NTP consumption, and these biochemical changes would correspond to impaired cognitive abilities. Methods: We used phosphorus-31 magnetic resonance spectroscopy to quantify high-energy phosphates. We performed the neuroimaging in conjunction with neurocognitive assessments targeting prefrontal cortex-mediated tasks. Results: Our results revealed significantly lower $gamma$-NTP levels in the athletes after concussion. Although the concussed and non-concussed participants performed similarly in neurocognitive assessments, lower levels of $gamma$-NTP were associated with worse scores on neurocognitive tasks. Conclusions: Our results support the concept of increased energy demand in the prefrontal cortex of a concussed brain, and we found that while neurocognitive assessments appear normal, brain energetics may be abnormal. A longitudinal study could help establish brain NTP levels as a biomarker to aid in diagnosis and to assess recovery in concussed patients. © 2015 Wolters Kluwer Health, Inc.},
keywords = {Adolescent, adult, Article, athlete, Athletic Injuries, biochemical analysis, bioenergy, brain concussion, clinical article, cognition, college, Concussion, energy consumption, Energy Metabolism, Female, high energy phosphate, human, Humans, Longitudinal studies, longitudinal study, Magnetic Resonance Spectroscopy, Male, metabolism, MR spectroscopy (phosphorus-31), neuroimaging, NTP, NUCLEAR magnetic resonance spectroscopy, nucleoside, nucleoside triphosphate, Nucleosides, Pathophysiology, phosphate, Phosphates, phosphorus, Phosphorus Isotopes, phosphorus nuclear magnetic resonance, PHYSIOLOGY, Prefrontal Cortex, priority journal, procedures, sport injury, Universities, university, Young Adult},
pubstate = {published},
tppubtype = {article}
}
Ojo, J O; Mouzon, B C; Crawford, F
Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men Journal Article
In: Experimental Neurology, vol. 275, pp. 389–404, 2016.
@article{Ojo2016,
title = {Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men},
author = {Ojo, J O and Mouzon, B C and Crawford, F},
doi = {10.1016/j.expneurol.2015.06.003},
year = {2016},
date = {2016-01-01},
journal = {Experimental Neurology},
volume = {275},
pages = {389--404},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been recognized as one of the major risk factors associated with CTE. Although these human studies have been informative, their retrospective design carries certain inherent limitations that should be cautiously interpreted. In particular, the current overriding issue in the CTE literature remains confusing in regard to appropriate definitions of terminology, variability in individual pathologies and the potential case selection bias in autopsy based studies. There are currently no epidemiological or prospective studies on CTE. Controlled preclinical studies in animals therefore provide an alternative means for specifically interrogating aspects of CTE pathogenesis. In this article, we review the current literature and discuss difficulties and challenges of developing in-vivo TBI experimental paradigms to explore the link between repetitive head trauma and tau-dependent changes. We provide our current opinion list of recommended features to consider for successfully modeling CTE in animals to better understand the pathobiology and develop therapeutics and diagnostics, and critical factors, which might influence outcome. We finally discuss the possible directions of future experimental research in the repetitive TBI/CTE field. © 2015 Elsevier Inc..},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Sikoglu, E M; Liso Navarro, A A; Czerniak, S M; McCafferty, J; Eisenstock, J; Stevenson, J H; King, J A; Moore, C M
Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study Journal Article
In: Cognitive and Behavioral Neurology, vol. 28, no. 4, pp. 181–187, 2015.
@article{Sikoglu2015,
title = {Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study},
author = {Sikoglu, E M and {Liso Navarro}, A A and Czerniak, S M and McCafferty, J and Eisenstock, J and Stevenson, J H and King, J A and Moore, C M},
doi = {10.1097/WNN.0000000000000076},
year = {2015},
date = {2015-01-01},
journal = {Cognitive and Behavioral Neurology},
volume = {28},
number = {4},
pages = {181--187},
abstract = {Background: Although clinical evaluations and neurocognitive assessments are commonly used to evaluate the extent of and recovery from concussion, brain bioenergetics could provide a more quantitative marker. The neurometabolic response to a concussion is thought to increase neuronal energy consumption and thus the demand for nucleoside triphosphate (NTP). Objective: We investigated the possible disruption in high-energy metabolism within the prefrontal cortex of college athletes who had either had a concussion within the past 6 months (n=14) or had never had a concussion (n=13). We hypothesized that concussed athletes would have imbalanced brain bioenergetics resulting from increased NTP consumption, and these biochemical changes would correspond to impaired cognitive abilities. Methods: We used phosphorus-31 magnetic resonance spectroscopy to quantify high-energy phosphates. We performed the neuroimaging in conjunction with neurocognitive assessments targeting prefrontal cortex-mediated tasks. Results: Our results revealed significantly lower $gamma$-NTP levels in the athletes after concussion. Although the concussed and non-concussed participants performed similarly in neurocognitive assessments, lower levels of $gamma$-NTP were associated with worse scores on neurocognitive tasks. Conclusions: Our results support the concept of increased energy demand in the prefrontal cortex of a concussed brain, and we found that while neurocognitive assessments appear normal, brain energetics may be abnormal. A longitudinal study could help establish brain NTP levels as a biomarker to aid in diagnosis and to assess recovery in concussed patients. © 2015 Wolters Kluwer Health, Inc.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ojo, J O; Mouzon, B C; Crawford, F
Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men Journal Article
In: Experimental Neurology, vol. 275, pp. 389–404, 2016.
Abstract | Links | BibTeX | Tags: amyloid beta protein, animal, Animal models, Animals, Astroglial tangles, Brain Injury, cell activation, Chronic, complication, Concussion, Craniocerebral Trauma, CTE, diffuse axonal injury, disease duration, disease model, Disease Models, genetic predisposition, gliosis, head injury, hippocampus, human, Humans, lifestyle modification, lithium, metabolism, Mice, microglia, minocycline, mouse, nervous system inflammation, Neurobehaviour, Neurofibrillary tangles, neuropathology, nonhuman, pathogenesis, pathology, priority journal, procedures, protein aggregation, protein analysis, protein blood level, protein cleavage, Repetitive TBI, Review, sex difference, stress activated protein kinase inhibitor, Systematic Review, Tau, tau protein, tau Proteins, Transgenic mice, Translational Medical Research, translational research, traumatic brain injury, trends
@article{Ojo2016,
title = {Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men},
author = {Ojo, J O and Mouzon, B C and Crawford, F},
doi = {10.1016/j.expneurol.2015.06.003},
year = {2016},
date = {2016-01-01},
journal = {Experimental Neurology},
volume = {275},
pages = {389--404},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been recognized as one of the major risk factors associated with CTE. Although these human studies have been informative, their retrospective design carries certain inherent limitations that should be cautiously interpreted. In particular, the current overriding issue in the CTE literature remains confusing in regard to appropriate definitions of terminology, variability in individual pathologies and the potential case selection bias in autopsy based studies. There are currently no epidemiological or prospective studies on CTE. Controlled preclinical studies in animals therefore provide an alternative means for specifically interrogating aspects of CTE pathogenesis. In this article, we review the current literature and discuss difficulties and challenges of developing in-vivo TBI experimental paradigms to explore the link between repetitive head trauma and tau-dependent changes. We provide our current opinion list of recommended features to consider for successfully modeling CTE in animals to better understand the pathobiology and develop therapeutics and diagnostics, and critical factors, which might influence outcome. We finally discuss the possible directions of future experimental research in the repetitive TBI/CTE field. © 2015 Elsevier Inc..},
keywords = {amyloid beta protein, animal, Animal models, Animals, Astroglial tangles, Brain Injury, cell activation, Chronic, complication, Concussion, Craniocerebral Trauma, CTE, diffuse axonal injury, disease duration, disease model, Disease Models, genetic predisposition, gliosis, head injury, hippocampus, human, Humans, lifestyle modification, lithium, metabolism, Mice, microglia, minocycline, mouse, nervous system inflammation, Neurobehaviour, Neurofibrillary tangles, neuropathology, nonhuman, pathogenesis, pathology, priority journal, procedures, protein aggregation, protein analysis, protein blood level, protein cleavage, Repetitive TBI, Review, sex difference, stress activated protein kinase inhibitor, Systematic Review, Tau, tau protein, tau Proteins, Transgenic mice, Translational Medical Research, translational research, traumatic brain injury, trends},
pubstate = {published},
tppubtype = {article}
}
Sikoglu, E M; Liso Navarro, A A; Czerniak, S M; McCafferty, J; Eisenstock, J; Stevenson, J H; King, J A; Moore, C M
Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study Journal Article
In: Cognitive and Behavioral Neurology, vol. 28, no. 4, pp. 181–187, 2015.
Abstract | Links | BibTeX | Tags: Adolescent, adult, Article, athlete, Athletic Injuries, biochemical analysis, bioenergy, brain concussion, clinical article, cognition, college, Concussion, energy consumption, Energy Metabolism, Female, high energy phosphate, human, Humans, Longitudinal studies, longitudinal study, Magnetic Resonance Spectroscopy, Male, metabolism, MR spectroscopy (phosphorus-31), neuroimaging, NTP, NUCLEAR magnetic resonance spectroscopy, nucleoside, nucleoside triphosphate, Nucleosides, Pathophysiology, phosphate, Phosphates, phosphorus, Phosphorus Isotopes, phosphorus nuclear magnetic resonance, PHYSIOLOGY, Prefrontal Cortex, priority journal, procedures, sport injury, Universities, university, Young Adult
@article{Sikoglu2015,
title = {Effects of Recent Concussion on Brain Bioenergetics: A Phosphorus-31 Magnetic Resonance Spectroscopy Study},
author = {Sikoglu, E M and {Liso Navarro}, A A and Czerniak, S M and McCafferty, J and Eisenstock, J and Stevenson, J H and King, J A and Moore, C M},
doi = {10.1097/WNN.0000000000000076},
year = {2015},
date = {2015-01-01},
journal = {Cognitive and Behavioral Neurology},
volume = {28},
number = {4},
pages = {181--187},
abstract = {Background: Although clinical evaluations and neurocognitive assessments are commonly used to evaluate the extent of and recovery from concussion, brain bioenergetics could provide a more quantitative marker. The neurometabolic response to a concussion is thought to increase neuronal energy consumption and thus the demand for nucleoside triphosphate (NTP). Objective: We investigated the possible disruption in high-energy metabolism within the prefrontal cortex of college athletes who had either had a concussion within the past 6 months (n=14) or had never had a concussion (n=13). We hypothesized that concussed athletes would have imbalanced brain bioenergetics resulting from increased NTP consumption, and these biochemical changes would correspond to impaired cognitive abilities. Methods: We used phosphorus-31 magnetic resonance spectroscopy to quantify high-energy phosphates. We performed the neuroimaging in conjunction with neurocognitive assessments targeting prefrontal cortex-mediated tasks. Results: Our results revealed significantly lower $gamma$-NTP levels in the athletes after concussion. Although the concussed and non-concussed participants performed similarly in neurocognitive assessments, lower levels of $gamma$-NTP were associated with worse scores on neurocognitive tasks. Conclusions: Our results support the concept of increased energy demand in the prefrontal cortex of a concussed brain, and we found that while neurocognitive assessments appear normal, brain energetics may be abnormal. A longitudinal study could help establish brain NTP levels as a biomarker to aid in diagnosis and to assess recovery in concussed patients. © 2015 Wolters Kluwer Health, Inc.},
keywords = {Adolescent, adult, Article, athlete, Athletic Injuries, biochemical analysis, bioenergy, brain concussion, clinical article, cognition, college, Concussion, energy consumption, Energy Metabolism, Female, high energy phosphate, human, Humans, Longitudinal studies, longitudinal study, Magnetic Resonance Spectroscopy, Male, metabolism, MR spectroscopy (phosphorus-31), neuroimaging, NTP, NUCLEAR magnetic resonance spectroscopy, nucleoside, nucleoside triphosphate, Nucleosides, Pathophysiology, phosphate, Phosphates, phosphorus, Phosphorus Isotopes, phosphorus nuclear magnetic resonance, PHYSIOLOGY, Prefrontal Cortex, priority journal, procedures, sport injury, Universities, university, Young Adult},
pubstate = {published},
tppubtype = {article}
}