Tracking the Silent Epidemic and Educating the Public

Langlois, Jean; Marr, Angela; Mitchko, Jane; Johnson, Renee L.

doi:10.1097/00001199-200505000-00003

Cited by 90 publications

(27 citation statements)

References 21 publications

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“…Mild traumatic brain injury (mTBI) has been called a “silent epidemic” as the initial symptoms can be so subtle that the majority of people who have experienced a concussion do not seek medical attention 1, 2. As a result, the consequences of repeated concussions/mTBI (r‐mTBI) have long been underestimated and viewed as a transient injury without long‐term consequences.…”

Section: Introductionmentioning

confidence: 99%

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Mouzon

Bachmeier

Ojo

et al. 2017

Ann Clin Transl Neurol

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ObjectiveExposure to repetitive concussion, or mild traumatic brain injury (mTBI), has been linked with increased risk of long‐term neurodegenerative changes, specifically chronic traumatic encephalopathy (CTE). To date, preclinical studies largely have focused on the immediate aftermath of mTBI, with no literature on the lifelong consequences of mTBI in these models. This study provides the first account of lifelong neurobehavioral and histological consequences of repetitive mTBI providing unique insight into the constellation of evolving and ongoing pathologies with late survival.MethodsMale C57BL/6J mice (aged 2–3 months) were exposed to either single or repetitive mild TBI or sham procedure. Thereafter, animals were monitored and assessed at 24 months post last injury for measures of motor coordination, learning deficits, cognitive function, and anxiety‐like behavior prior to euthanasia and preparation of the brains for detailed neuropathological and protein biochemical studies.ResultsAt 24 months survival animals exposed to r‐mTBI showed clear evidence of learning and working memory impairment with a lack of spatial memory and vestibule‐motor vestibulomotor deficits compared to sham animals. Associated with these late behavioral deficits there was evidence of ongoing axonal degeneration and neuroinflammation in subcortical white matter tracts. Notably, these changes were also observed after a single mTBI, albeit to a lesser degree than repetitive mTBI.InterpretationIn this context, our current data demonstrate, for the first time, that rather than an acute, time limited event, mild TBI can precipitate a lifelong degenerative process. These data therefore suggest that successful treatment strategies should consider both the acute and chronic nature of mTBI.

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Section: Introductionmentioning

confidence: 99%

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Mouzon

Bachmeier

Ojo

et al. 2017

Ann Clin Transl Neurol

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“…Traumatic brain injury (TBI) is a prevalent healthcare concern with an estimated 1.7 million cases occurring annually in the US alone 1, 2 . In addition to civilian sports-related injuries, motor vehicles accidents, and falls, recent warfare has increased the number of Veterans experiencing TBI, further demonstrating the need for effective therapeutics that can be administered acutely following injury in the field 3, 4 .…”

Section: Introductionmentioning

confidence: 99%

Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury

Lutton

Razmpour

Andrews

et al. 2017

Sci Rep

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Traumatic brain injury (TBI) contributes to one third of injury related deaths in the US. Treatment strategies for TBI are supportive, and the pathophysiology is not fully understood. Secondary mechanisms of injury in TBI, such as oxidative stress and inflammation, are points at which intervention may reduce neuropathology. Evidence suggests that reactive oxygen species (ROS) propagate blood-brain barrier (BBB) hyperpermeability and inflammation following TBI. We hypothesized that targeted detoxification of ROS may improve the pathological outcomes of TBI. Following TBI, endothelial activation results in a time dependent increase in vascular expression of ICAM-1. We conjugated catalase to anti-ICAM-1 antibodies and administered the conjugate to 8 wk old C57BL/6J mice 30 min after moderate controlled cortical impact injury. Results indicate that catalase targeted to ICAM-1 reduces markers of oxidative stress, preserves BBB permeability, and attenuates neuropathological indices more effectively than non-targeted catalase and anti-ICAM-1 antibody alone. Furthermore, the study of microglia by two-photon microscopy revealed that anti-ICAM-1/catalase prevents the transition of microglia to an activated phenotype. These findings demonstrate the use of a targeted antioxidant enzyme to interfere with oxidative stress mechanisms in TBI and provide a proof-of-concept approach to improve acute TBI management that may also be applicable to other neuroinflammatory conditions.

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“…Millions of individuals suffer TBI each year resulting in long term disabilities, with many requiring hospitalization [1]. A majority of TBI survivors have chronic neurobehavioral problems including cognitive deficits.…”

Section: Introductionmentioning

confidence: 99%

A time course of NADPH-oxidase up-regulation and endothelial nitric oxide synthase activation in the hippocampus following neurotrauma

Ansari

Roberts

Scheff

2014

Free Radical Biology and Medicine

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Nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase; NOX) is a complex enzyme responsible for increased levels of reactive oxygen species (ROS), superoxide (O2.−). NOX derived O2.− is a key player in oxidative stress and inflammation mediated multiple secondary injury cascades (SIC) following traumatic brain injury (TBI). The O2.− reacts with nitric oxide (NO), produces various reactive nitrogen species (RNS), and contributes to apoptotic cell death. Following a unilateral cortical contusion, young adult rats were killed at various times post injury (1, 3, 6, 12, 24, 48, 72, and 96 h). Fresh tissue from the hippocampus was analyzed for NOX activity, and level of O2.−. In addition we evaluated the translocation of cytosolic NOX proteins (p67Phox, p47Phox and p40Phox) to the membrane, along with total NO and the activation (phosphorylation) of endothelial nitric oxide synthase (p-eNOS). Results show that both enzymes and levels of O2.− and NO have time dependent injury effects in the hippocampus. Translocation of cytosolic NOX proteins into membrane, NOX activity and O2.− were also increased in a time dependent fashion. Both, NOX activity and O2.− were increased at 6 h. Levels of p-eNOS increased within 1 h, with significant elevation of NO at 12 h post TBI. Levels of NO failed to show a significant association with p-eNOS, but did associate with O2.−. NOX up-regulation strongly associated with both the levels of O2.− and also total NO. The initial 12 hours post TBI are very important as a possible window of opportunity to interrupt SIC. It may be important to selectively target the translocation of cytosolic subunits for the modulation of NOX function.

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Tracking the Silent Epidemic and Educating the Public

Cited by 90 publications

References 21 publications

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Lifelong behavioral and neuropathological consequences of repetitive mild traumatic brain injury

Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury

A time course of NADPH-oxidase up-regulation and endothelial nitric oxide synthase activation in the hippocampus following neurotrauma

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