scholarly journals Repetitive Traumatic Brain Injury Causes Neuroinflammation before Tau Pathology in Adolescent P301S Mice

2021 ◽  
Vol 22 (2) ◽  
pp. 907
Author(s):  
Saef Izzy ◽  
Alexander Brown-Whalen ◽  
Taha Yahya ◽  
Aliyah Sarro-Schwartz ◽  
Gina Jin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Outcomes ◽  
Closed Head Injury ◽  
Tau Pathology ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Tau Mutation ◽  
Injury Causes

Repetitive closed head injury (rCHI) is commonly encountered in young athletes engaged in contact and collision sports. Traumatic brain injury (TBI) including rCHI has been reported to be an important risk factor for several tauopathies in studies of adult humans and animals. However, the link between rCHI and the progression of tau pathology in adolescents remains to be elucidated. We evaluated whether rCHI can trigger the initial acceleration of pathological tau in adolescent mice and impact the long-term outcomes post-injury. To this end, we subjected adolescent transgenic mice expressing the P301S tau mutation to mild rCHI and assessed tau hyperphosphorylation, tangle formation, markers of neuroinflammation, and behavioral deficits at 40 days post rCHI. We report that rCHI did not accelerate tau pathology and did not worsen behavioral outcomes compared to control mice. However, rCHI induced cortical and hippocampal microgliosis and corpus callosum astrocytosis in P301S mice by 40 days post-injury. In contrast, we did not find significant microgliosis or astrocytosis after rCHI in age-matched WT mice or sham-injured P301S mice. Our data suggest that neuroinflammation precedes the development of Tau pathology in this rCHI model of adolescent repetitive mild TBI.

scholarly journals 3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury

2021 ◽  
Vol 22 (15) ◽  
pp. 8276
Author(s):  
Pen-Sen Huang ◽  
Ping-Yen Tsai ◽  
Ling-Yu Yang ◽  
Daniela Lecca ◽  
Weiming Luo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Short Term Memory ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Cognitive Behaviors ◽  
Moderate Traumatic Brain Injury ◽  
Short And Long Term ◽  
Behavioral Impairments ◽  
Hippocampal Neurodegeneration

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

scholarly journals Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0161053 ◽  
Author(s):  
Natalia M. Grin’kina ◽  
Yang Li ◽  
Margalit Haber ◽  
Michael Sangobowale ◽  
Elena Nikulina ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Behavioral Outcomes ◽  
Head Model ◽  
Closed Head ◽  
Righting Reflex

scholarly journals Long-Term Survival Following Traumatic Brain Injury: A Population-Based Parametric Survival Analysis

2016 ◽  
Vol 47 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Gordon W. Fuller ◽  
Jeanine Ransom ◽  
Jay Mandrekar ◽  
Allen W. Brown
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
General Population ◽  
Life Expectancy ◽  
Health Planning ◽  
Population Based ◽  
Post Injury ◽  
Term Survival ◽  
Parametric Survival

Background: Long-term mortality may be increased following traumatic brain injury (TBI); however, the degree to which survival could be reduced is unknown. We aimed at modelling life expectancy following post-acute TBI to provide predictions of longevity and quantify differences in survivorship with the general population. Methods: A population-based retrospective cohort study using data from the Rochester Epidemiology Project (REP) was performed. A random sample of patients from Olmsted County, Minnesota with a confirmed TBI between 1987 and 2000 was identified and vital status determined in 2013. Parametric survival modelling was then used to develop a model to predict life expectancy following TBI conditional on age at injury. Survivorship following TBI was also compared with the general population and age- and gender-matched non-head injured REP controls. Results: Seven hundred and sixty nine patients were included in complete case analyses. The median follow-up time was 16.1 years (interquartile range 9.0-20.4) with 120 deaths occurring in the cohort during the study period. Survival after acute TBI was well represented by a Gompertz distribution. Victims of TBI surviving for at least 6 months post-injury demonstrated a much higher ongoing mortality rate compared to the US general population and non-TBI controls (hazard ratio 1.47, 95% CI 1.15-1.87). US general population cohort life table data was used to update the Gompertz model's shape and scale parameters to account for cohort effects and allow prediction of life expectancy in contemporary TBI. Conclusions: Survivors of TBI have decreased life expectancy compared to the general population. This may be secondary to the head injury itself or result from patient characteristics associated with both the propensity for TBI and increased early mortality. Post-TBI life expectancy estimates may be useful to guide prognosis, in public health planning, for actuarial applications and in the extrapolation of outcomes for TBI economic models.

scholarly journals Exosomal MicroRNA Differential Expression in Plasma of Young Adults with Chronic Mild Traumatic Brain Injury and Healthy Control

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Rany Vorn ◽  
Maiko Suarez ◽  
Jacob C. White ◽  
Carina A. Martin ◽  
Hyung-Suk Kim ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Young Adults ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Pathophysiological Mechanism ◽  
Post Injury ◽  
Persistent Symptoms ◽  
Healthy Control ◽  
Underlying Mechanisms

Chronic mild traumatic brain injury (mTBI) has long-term consequences, such as neurological disability, but its pathophysiological mechanism is unknown. Exosomal microRNAs (exomiRNAs) may be important mediators of molecular and cellular changes involved in persistent symptoms after mTBI. We profiled exosomal microRNAs (exomiRNAs) in plasma from young adults with or without a chronic mTBI to decipher the underlying mechanisms of its long-lasting symptoms after mTBI. We identified 25 significantly dysregulated exomiRNAs in the chronic mTBI group (n = 29, with 4.48 mean years since the last injury) compared to controls (n = 11). These miRNAs are associated with pathways of neurological disease, organismal injury and abnormalities, and psychological disease. Dysregulation of these plasma exomiRNAs in chronic mTBI may indicate that neuronal inflammation can last long after the injury and result in enduring and persistent post-injury symptoms. These findings are useful for diagnosing and treating chronic mTBIs.

scholarly journals Outcomes after Complicated and Uncomplicated Mild Traumatic Brain Injury at Three-and Six-Months Post-Injury: Results from the CENTER-TBI Study

2020 ◽  
Vol 9 (5) ◽  
pp. 1525 ◽  
Author(s):  
Daphne C. Voormolen ◽  
Marina Zeldovich ◽  
Juanita A. Haagsma ◽  
Suzanne Polinder ◽  
Sarah Friedrich ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Functional Outcome ◽  
Mild Traumatic Brain Injury ◽  
Intracranial Injury ◽  
Post Injury ◽  
Long Term Outcome ◽  
Sf 36 ◽  
Disease Specific

The objective of this study was to provide a comprehensive examination of the relation of complicated and uncomplicated mild traumatic brain injury (mTBI) with multidimensional outcomes at three- and six-months after TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) research project. Patients after mTBI (Glasgow Coma scale (GCS) score of 13–15) enrolled in the study were differentiated into two groups based on computed tomography (CT) findings: complicated mTBI (presence of any traumatic intracranial injury on first CT) and uncomplicated mTBI (absence of any traumatic intracranial injury on first CT). Multidimensional outcomes were assessed using seven instruments measuring generic and disease-specific health-related quality of life (HRQoL) (SF-36 and QOLIBRI), functional outcome (GOSE), and psycho-social domains including symptoms of post-traumatic stress disorder (PTSD) (PCL-5), depression (PHQ-9), and anxiety (GAD-7). Data were analyzed using a multivariate repeated measures approach (MANOVA-RM), which inspected mTBI groups at three- and six-months post injury. Patients after complicated mTBI had significantly lower GOSE scores, reported lower physical and mental component summary scores based on the SF-36 version 2, and showed significantly lower HRQoL measured by QOLIBRI compared to those after uncomplicated mTBI. There was no difference between mTBI groups when looking at psychological outcomes, however, a slight improvement in PTSD symptoms and depression was observed for the entire sample from three to six months. Patients after complicated mTBI reported lower generic and disease specific HRQoL and worse functional outcome compared to individuals after uncomplicated mTBI at three and six months. Both groups showed a tendency to improve from three to six months after TBI. The complicated mTBI group included more patients with an impaired long-term outcome than the uncomplicated group. Nevertheless, patients, clinicians, researchers, and decisions-makers in health care should take account of the short and long-term impact on outcome for patients after both uncomplicated and complicated mTBI.

TP2-3 Long-term survival and five year hospital resource usage following traumatic brain injury in scotland from 1997–2015: a population-based retrospective cohort study

2019 ◽  
Vol 90 (3) ◽  
pp. e14.2-e14
Author(s):  
JJM Loan ◽  
NW Scott ◽  
JO Jansen
Keyword(s):  
Traumatic Brain Injury ◽  
Cohort Study ◽  
Brain Injury ◽  
Population Based ◽  
Resource Usage ◽  
Hospital Resource ◽  
Post Injury ◽  
Term Survival ◽  
Long Term Survival

AimTo determine if survival and hospital resource usage differ following traumatic brain injury (TBI) compared with head injury without neurological injury(HI).MethodsThis retrospective population-based cohort study included all 25 319 patients admitted to a Scottish NHS hospital from 1997–2015 with TBI. Participants were identified using previously validated ICD-10 based definitions. For comparison, all 194 049 HI cases were identified. Our main outcome measures were hazards of all-cause mortality after TBI, compared with HI, over 18 years follow-up period; and odds of mortality at one month post-injury. Number of days spent as inpatients and number of outpatient attendances per surviving month post-injury were used as measures of resource utilisation.ResultsThe adjusted odds ratio for mortality in the first month post-injury for TBI was 7.12 (95% confidence interval [CI] 6.73–7.52; p<0.001). For the remaining 18 year study period, the hazards of morality after TBI were 0.93 (CI 0.90–0.96; p<0.001). TBI was associated with 2.15 (CI 2.10–2.20; p<0.001) more days spent as inpatient and 1.09 times more outpatient attendances (CI 1.07–1.11; p<0.001) than HI.ConclusionsAlthough initial mortality following TBI is high, survivors of the first month can achieve comparable long-term survival to HI. However this is associated with increased utilisation of hospital services in the TBI group.

scholarly journals PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 3265-3279 ◽  
Author(s):  
Keisuke Takahata ◽  
Yasuyuki Kimura ◽  
Naruhiko Sahara ◽  
Shunsuke Koga ◽  
Hitoshi Shimada ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Late Onset ◽  
Neuropsychiatric Symptoms ◽  
Tau Pathology ◽  
Long Term Outcomes

Is tau load associated with long-term outcomes of TBI? By using PET to assess tau deposits in patients with chronic TBI, Takahata et al. reveal elevated tau load compared to age-matched controls, and show that the abundance of tau in white matter is associated with late-onset neuropsychiatric symptoms.

scholarly journals Increased Vulnerability of NFH-LacZ Transgenic Mouse to Traumatic Brain Injury-Induced Behavioral Deficits and Cortical Damage

1999 ◽  
Vol 19 (7) ◽  
pp. 762-770 ◽  
Author(s):  
Michio Nakamura ◽  
Kathryn E. Saatman ◽  
James E. Galvin ◽  
Uwe Scherbel ◽  
Ramesh Raghupathi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Motor Dysfunction ◽  
Tissue Loss ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Beam Balance ◽  
Brain Injured ◽  
Neuromotor Function ◽  
Histopathologic Analysis

The authors evaluated the neurobehavioral and neuropathologic sequelae after traumatic brain injury (TBI) in transgenic (TG) mice expressing truncated high molecular weight neurofilament (NF) protein fused to beta-galactosidase (NFH-LacZ), which develop Lewy body-like NF-rich inclusions throughout the CNS. TG mice and their wild-type (WT) littermates were subjected to controlled cortical impact brain injury (TG, n=19; WT, n=17) or served as uninjured controls (TG, n =11; WT, n =11). During a 3-week period, mice were evaluated with an array of neuromotor function tests including neuroscore, beam balance, and both fast and slow acceleration rotarod. Brain-injured WT and TG mice showed significant motor dysfunction until 15 days and 21 days post-injury, respectively ( P < .025). Compared with brain-injured WT mice, brain-injured TG mice had significantly greater motor dysfunction as assessed by neuroscore ( P < .01) up to and including 15 days post-injury. Similarly, brain-injured TG mice performed significantly worse than brain-injured WT mice on slow acceleration rotarod at 2, 8, and 15 days post-injury ( P < .05), and beam balance over 2 weeks post-injury ( P < .01). Histopathologic analysis showed significantly greater tissue loss in the injured hemisphere in TG mice at 4 weeks post-injury ( P < .01). Together these data show that NFH-LacZ TG mice are more behaviorally and histologically vulnerable to TBI than WT mice, suggesting that the presence of NF-rich inclusions may exacerbate neuromotor dysfunction and cell death after TBI.

Addressing the Sexual Concerns of Persons With Traumatic Brain Injury in Rehabilitation Settings: A Framework for Action

2001 ◽  
Vol 2 (2) ◽  
pp. 97-108 ◽  
Author(s):  
Grahame Simpson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
World Health Organisation ◽  
World Health ◽  
Post Injury ◽  
Rehabilitation Programs ◽  
Human Functioning ◽  
Sexual Concerns ◽  
Organisational Structures

AbstractTraumatic brain injury (TBI) impacts upon people's sexuality with 50% to 60% of persons reporting some level of disruption post-injury. However, only small proportions of patients/family members report that rehabilitation health professionals made inquiries about whether they had any sexual concerns. Rehabilitation programs have a responsibility to meet the challenge of addressing this important area of human functioning. An agency framework is described that provides a non-threatening, structured way for services to conceptualise, introduce or upgrade sexuality services in a manner that can be maintained over the long term. The framework contains an underlying philosophy of sexuality, five proposed modalities of service provision and detail of the underlying organisational structures that are required to provide sexuality services with consistency and effectiveness over the long term. Finally, organisational strategies that can be employed to implement the framework are discussed as well as suggestions about the sequencing of such strategies. By using the framework, rehabilitation services can put sexuality back onto their treatment agenda, as they seek to restore patients/clients with TBI to the “highest level of adaptation attainable” (World Health Organisation, 1996, p. 1) in all areas of their lives.

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