Lucke-Wold, B P; Naser, Z J; Logsdon, A F; Turner, R C; Smith, K E; Robson, M J; Bailes, J E; Lee, J M; Rosen, C L; Huber, J D
Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury Journal Article
In: Translational Research: The Journal Of Laboratory & Clinical Medicine, vol. 166, no. 6, pp. 509–528.e1, 2015.
Abstract | BibTeX | Tags: *Blast Injuries/pa [Pathology], *Brain Injuries/pa [Pathology], *NADPH Oxidase/me [Metabolism], *Oxidative Stress, 73Y7P0K73Y (Thioctic Acid), Animals, Apoptosis, Blast Injuries/en [Enzymology], Blast Injuries/me [Metabolism], Brain Injuries/en [Enzymology], Brain Injuries/me [Metabolism], EC 1-6-3-1 (NADPH Oxidase), Male, Rats, Sprague-Dawley, Thioctic Acid/pd [Pharmacology]
@article{Lucke-Wold2015,
title = {Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury},
author = {Lucke-Wold, B P and Naser, Z J and Logsdon, A F and Turner, R C and Smith, K E and Robson, M J and Bailes, J E and Lee, J M and Rosen, C L and Huber, J D},
year = {2015},
date = {2015-01-01},
journal = {Translational Research: The Journal Of Laboratory \& Clinical Medicine},
volume = {166},
number = {6},
pages = {509--528.e1},
abstract = {A total of 1.7 million traumatic brain injuries (TBIs) occur each year in the United States, but available pharmacologic options for the treatment of acute neurotrauma are limited. Oxidative stress is an important secondary mechanism of injury that can lead to neuronal apoptosis and subsequent behavioral changes. Using a clinically relevant and validated rodent blast model, we investigated how nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression and associated oxidative stress contribute to cellular apoptosis after single and repeat blast injuries. Nox4 forms a complex with p22phox after injury, forming free radicals at neuronal membranes. Using immunohistochemical-staining methods, we found a visible increase in Nox4 after single blast injury in Sprague Dawley rats. Interestingly, Nox4 was also increased in postmortem human samples obtained from athletes diagnosed with chronic traumatic encephalopathy. Nox4 activity correlated with an increase in superoxide formation. Alpha-lipoic acid, an oxidative stress inhibitor, prevented the development of superoxide acutely and increased antiapoptotic markers B-cell lymphoma 2 (t = 3.079, P \< 0.05) and heme oxygenase 1 (t = 8.169, P \< 0.001) after single blast. Subacutely, alpha-lipoic acid treatment reduced proapoptotic markers Bax (t = 4.483, P \< 0.05), caspase 12 (t = 6.157, P \< 0.001), and caspase 3 (t = 4.573, P \< 0.01) after repetitive blast, and reduced tau hyperphosphorylation indicated by decreased CP-13 and paired helical filament staining. Alpha-lipoic acid ameliorated impulsive-like behavior 7 days after repetitive blast injury (t = 3.573, P \< 0.05) compared with blast exposed animals without treatment. TBI can cause debilitating symptoms and psychiatric disorders. Oxidative stress is an ideal target for neuropharmacologic intervention, and alpha-lipoic acid warrants further investigation as a therapeutic for prevention of chronic neurodegeneration. Copyright © 2015 Elsevier Inc. All rights reserved.},
keywords = {*Blast Injuries/pa [Pathology], *Brain Injuries/pa [Pathology], *NADPH Oxidase/me [Metabolism], *Oxidative Stress, 73Y7P0K73Y (Thioctic Acid), Animals, Apoptosis, Blast Injuries/en [Enzymology], Blast Injuries/me [Metabolism], Brain Injuries/en [Enzymology], Brain Injuries/me [Metabolism], EC 1-6-3-1 (NADPH Oxidase), Male, Rats, Sprague-Dawley, Thioctic Acid/pd [Pharmacology]},
pubstate = {published},
tppubtype = {article}
}
Omalu, B; Hammers, J L; Bailes, J; Hamilton, R L; Kamboh, M I; Webster, G; Fitzsimmons, R P
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide Journal Article
In: Neurosurgical Focus, vol. 31, no. 5, pp. E3, 2011.
Abstract | BibTeX | Tags: *Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention & Control]
@article{Omalu2011,
title = {Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide},
author = {Omalu, B and Hammers, J L and Bailes, J and Hamilton, R L and Kamboh, M I and Webster, G and Fitzsimmons, R P},
year = {2011},
date = {2011-01-01},
journal = {Neurosurgical Focus},
volume = {31},
number = {5},
pages = {E3},
abstract = {Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.},
keywords = {*Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention \& Control]},
pubstate = {published},
tppubtype = {article}
}
Lucke-Wold, B P; Naser, Z J; Logsdon, A F; Turner, R C; Smith, K E; Robson, M J; Bailes, J E; Lee, J M; Rosen, C L; Huber, J D
Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury Journal Article
In: Translational Research: The Journal Of Laboratory & Clinical Medicine, vol. 166, no. 6, pp. 509–528.e1, 2015.
@article{Lucke-Wold2015,
title = {Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury},
author = {Lucke-Wold, B P and Naser, Z J and Logsdon, A F and Turner, R C and Smith, K E and Robson, M J and Bailes, J E and Lee, J M and Rosen, C L and Huber, J D},
year = {2015},
date = {2015-01-01},
journal = {Translational Research: The Journal Of Laboratory \& Clinical Medicine},
volume = {166},
number = {6},
pages = {509--528.e1},
abstract = {A total of 1.7 million traumatic brain injuries (TBIs) occur each year in the United States, but available pharmacologic options for the treatment of acute neurotrauma are limited. Oxidative stress is an important secondary mechanism of injury that can lead to neuronal apoptosis and subsequent behavioral changes. Using a clinically relevant and validated rodent blast model, we investigated how nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression and associated oxidative stress contribute to cellular apoptosis after single and repeat blast injuries. Nox4 forms a complex with p22phox after injury, forming free radicals at neuronal membranes. Using immunohistochemical-staining methods, we found a visible increase in Nox4 after single blast injury in Sprague Dawley rats. Interestingly, Nox4 was also increased in postmortem human samples obtained from athletes diagnosed with chronic traumatic encephalopathy. Nox4 activity correlated with an increase in superoxide formation. Alpha-lipoic acid, an oxidative stress inhibitor, prevented the development of superoxide acutely and increased antiapoptotic markers B-cell lymphoma 2 (t = 3.079, P \< 0.05) and heme oxygenase 1 (t = 8.169, P \< 0.001) after single blast. Subacutely, alpha-lipoic acid treatment reduced proapoptotic markers Bax (t = 4.483, P \< 0.05), caspase 12 (t = 6.157, P \< 0.001), and caspase 3 (t = 4.573, P \< 0.01) after repetitive blast, and reduced tau hyperphosphorylation indicated by decreased CP-13 and paired helical filament staining. Alpha-lipoic acid ameliorated impulsive-like behavior 7 days after repetitive blast injury (t = 3.573, P \< 0.05) compared with blast exposed animals without treatment. TBI can cause debilitating symptoms and psychiatric disorders. Oxidative stress is an ideal target for neuropharmacologic intervention, and alpha-lipoic acid warrants further investigation as a therapeutic for prevention of chronic neurodegeneration. Copyright © 2015 Elsevier Inc. All rights reserved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Omalu, B; Hammers, J L; Bailes, J; Hamilton, R L; Kamboh, M I; Webster, G; Fitzsimmons, R P
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide Journal Article
In: Neurosurgical Focus, vol. 31, no. 5, pp. E3, 2011.
@article{Omalu2011,
title = {Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide},
author = {Omalu, B and Hammers, J L and Bailes, J and Hamilton, R L and Kamboh, M I and Webster, G and Fitzsimmons, R P},
year = {2011},
date = {2011-01-01},
journal = {Neurosurgical Focus},
volume = {31},
number = {5},
pages = {E3},
abstract = {Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lucke-Wold, B P; Naser, Z J; Logsdon, A F; Turner, R C; Smith, K E; Robson, M J; Bailes, J E; Lee, J M; Rosen, C L; Huber, J D
Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury Journal Article
In: Translational Research: The Journal Of Laboratory & Clinical Medicine, vol. 166, no. 6, pp. 509–528.e1, 2015.
Abstract | BibTeX | Tags: *Blast Injuries/pa [Pathology], *Brain Injuries/pa [Pathology], *NADPH Oxidase/me [Metabolism], *Oxidative Stress, 73Y7P0K73Y (Thioctic Acid), Animals, Apoptosis, Blast Injuries/en [Enzymology], Blast Injuries/me [Metabolism], Brain Injuries/en [Enzymology], Brain Injuries/me [Metabolism], EC 1-6-3-1 (NADPH Oxidase), Male, Rats, Sprague-Dawley, Thioctic Acid/pd [Pharmacology]
@article{Lucke-Wold2015,
title = {Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury},
author = {Lucke-Wold, B P and Naser, Z J and Logsdon, A F and Turner, R C and Smith, K E and Robson, M J and Bailes, J E and Lee, J M and Rosen, C L and Huber, J D},
year = {2015},
date = {2015-01-01},
journal = {Translational Research: The Journal Of Laboratory \& Clinical Medicine},
volume = {166},
number = {6},
pages = {509--528.e1},
abstract = {A total of 1.7 million traumatic brain injuries (TBIs) occur each year in the United States, but available pharmacologic options for the treatment of acute neurotrauma are limited. Oxidative stress is an important secondary mechanism of injury that can lead to neuronal apoptosis and subsequent behavioral changes. Using a clinically relevant and validated rodent blast model, we investigated how nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression and associated oxidative stress contribute to cellular apoptosis after single and repeat blast injuries. Nox4 forms a complex with p22phox after injury, forming free radicals at neuronal membranes. Using immunohistochemical-staining methods, we found a visible increase in Nox4 after single blast injury in Sprague Dawley rats. Interestingly, Nox4 was also increased in postmortem human samples obtained from athletes diagnosed with chronic traumatic encephalopathy. Nox4 activity correlated with an increase in superoxide formation. Alpha-lipoic acid, an oxidative stress inhibitor, prevented the development of superoxide acutely and increased antiapoptotic markers B-cell lymphoma 2 (t = 3.079, P \< 0.05) and heme oxygenase 1 (t = 8.169, P \< 0.001) after single blast. Subacutely, alpha-lipoic acid treatment reduced proapoptotic markers Bax (t = 4.483, P \< 0.05), caspase 12 (t = 6.157, P \< 0.001), and caspase 3 (t = 4.573, P \< 0.01) after repetitive blast, and reduced tau hyperphosphorylation indicated by decreased CP-13 and paired helical filament staining. Alpha-lipoic acid ameliorated impulsive-like behavior 7 days after repetitive blast injury (t = 3.573, P \< 0.05) compared with blast exposed animals without treatment. TBI can cause debilitating symptoms and psychiatric disorders. Oxidative stress is an ideal target for neuropharmacologic intervention, and alpha-lipoic acid warrants further investigation as a therapeutic for prevention of chronic neurodegeneration. Copyright © 2015 Elsevier Inc. All rights reserved.},
keywords = {*Blast Injuries/pa [Pathology], *Brain Injuries/pa [Pathology], *NADPH Oxidase/me [Metabolism], *Oxidative Stress, 73Y7P0K73Y (Thioctic Acid), Animals, Apoptosis, Blast Injuries/en [Enzymology], Blast Injuries/me [Metabolism], Brain Injuries/en [Enzymology], Brain Injuries/me [Metabolism], EC 1-6-3-1 (NADPH Oxidase), Male, Rats, Sprague-Dawley, Thioctic Acid/pd [Pharmacology]},
pubstate = {published},
tppubtype = {article}
}
Omalu, B; Hammers, J L; Bailes, J; Hamilton, R L; Kamboh, M I; Webster, G; Fitzsimmons, R P
Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide Journal Article
In: Neurosurgical Focus, vol. 31, no. 5, pp. E3, 2011.
Abstract | BibTeX | Tags: *Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention & Control]
@article{Omalu2011,
title = {Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide},
author = {Omalu, B and Hammers, J L and Bailes, J and Hamilton, R L and Kamboh, M I and Webster, G and Fitzsimmons, R P},
year = {2011},
date = {2011-01-01},
journal = {Neurosurgical Focus},
volume = {31},
number = {5},
pages = {E3},
abstract = {Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.},
keywords = {*Blast Injuries/pa [Pathology], *Blast Injuries/pp [Physiopathology], *Brain Injury, *Combat Disorders/pp [Physiopathology], *Suicide/px [Psychology], 2003-2011, adult, Blast Injuries/co [Complications], Brain Injury, Chronic/co [Complications], Chronic/pa [Pathology], Chronic/pp [Physiopathology], Combat Disorders/px [Psychology], Humans, Iraq War, Male, Post-Traumatic/pp [Physiopatholo, Post-Traumatic/px [Psychology], Stress Disorders, Suicide/pc [Prevention \& Control]},
pubstate = {published},
tppubtype = {article}
}