Combined Effects of Repetitive Mild Traumatic Brain Injury and Alcohol Drinking on the Neuroinflammatory Cytokine Response and Cognitive Behavioral Outcomes

The relationship between alcohol consumption and traumatic brain injury (TBI) often focuses on alcohol consumption increasing the likelihood of incurring a TBI, rather than alcohol use outcomes after TBI. However, patients without a history of an alcohol use disorder can also show increased problem drinking after single or multiple TBIs. Alcohol and mild TBI share diffuse deleterious neurological impacts and cognitive impairments; therefore, the purpose of these studies was to determine if an interaction on brain and behavior outcomes occurs when alcohol is consumed longitudinally after TBI. To examine the impact of mild repetitive TBI (rmTBI) on voluntary alcohol consumption, mice were subjected to four mild TBI or sham procedures over a 2 week period, then offered alcohol (20% v/v) for 2 weeks using the two-bottle choice, drinking in the dark protocol. Following the drinking period, mice were evaluated for neuroinflammatory cytokine response or tested for cognitive and behavioral deficits. Results indicate no difference in alcohol consumption or preference following rmTBI as compared to sham; however, increases in the neuroinflammatory cytokine response due to alcohol consumption and some mild cognitive behavioral deficits after rmTBI and alcohol consumption were observed. These data suggest that the cytokine response to alcohol drinking and rmTBI + alcohol drinking is not necessarily aggregate, but the combination does result in an exacerbation of cognitive behavioral outcomes.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22020907 ◽

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.

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Alcohol Consumption Does not Impede Recovery from Mild to Moderate Traumatic Brain Injury

Journal of the International Neuropsychological Society ◽

10.1017/s1355617716000692 ◽

2016 ◽

Vol 22 (8) ◽

pp. 816-827 ◽

Cited By ~ 2

Author(s):

Noah D. Silverberg ◽

William Panenka ◽

Grant L. Iverson ◽

Jeffrey R. Brubacher ◽

Jason R. Shewchuk ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Alcohol Consumption ◽

Alcohol Use ◽

Diffusion Tensor ◽

Alcohol Intoxication ◽

Post Injury ◽

Term Outcome ◽

Long Term Outcome ◽

Moderate Traumatic Brain Injury

AbstractObjectives: To examine the effect of pre-injury alcohol use, acute alcohol intoxication, and post-injury alcohol use on outcome from mild to moderate traumatic brain injury (TBI). Methods: Prospective inception cohort of patients who presented to the Emergency Department with mild to moderate TBI and had a blood alcohol level (BAL) taken for clinical purposes. Those who completed the 1-year outcome assessment were eligible for this study (N=91). Outcomes of interest were the count of post-concussion symptoms (British Columbia Post-Concussion Symptom Inventory), low neuropsychological test scores (Neuropsychological Assessment Battery), and abnormal regions of interest on diffusion tensor imaging (low fractional anisotropy). The main predictors were pre-injury alcohol consumption (Cognitive Lifetime Drinking History interview), BAL, and post-injury alcohol use. Results: The alcohol use variables were moderately to strongly inter-correlated. None of the alcohol use variables (whether continuous or categorical) were related to 1-year TBI outcomes in generalized linear modeling. Participants in this cohort generally had a good clinical outcome, regardless of their pre-, peri-, and post-injury alcohol use. Conclusions: Alcohol may not significantly alter long-term outcome from mild to moderate TBI. (JINS, 2016, 22, 816–827)

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The impact of traumatic brain injury on developmental functioning in children: Mild TBI at home and school

PsycEXTRA Dataset ◽

10.1037/e556572013-079 ◽

2012 ◽

Author(s):

Rosalind Case ◽

Nicola Starkey ◽

Suzanne Barker-Collo ◽

Kelly Jones

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Tbi ◽

Developmental Functioning ◽

The Impact ◽

Home And School ◽

At Home

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Can Cognitive Behavioral Therapy for Insomnia also treat fatigue, pain, and mood symptoms in individuals with traumatic brain injury? – A multiple case report

Neurorehabilitation ◽

10.3233/nre-151296 ◽

2016 ◽

Vol 38 (1) ◽

pp. 59-69 ◽

Cited By ~ 18

Author(s):

William Lu ◽

Jason W. Krellman ◽

Marcel P. Dijkers

Keyword(s):

Traumatic Brain Injury ◽

Case Report ◽

Brain Injury ◽

Cognitive Behavioral Therapy ◽

Behavioral Therapy ◽

Cognitive Behavioral ◽

Mood Symptoms ◽

Multiple Case

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

International Journal of Molecular Sciences ◽

10.3390/ijms22158276 ◽

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.

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

PLoS ONE ◽

10.1371/journal.pone.0161053 ◽

2016 ◽

Vol 11 (9) ◽

pp. e0161053 ◽

Cited By ~ 8

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

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Development of prognostic models for Health-Related Quality of Life following traumatic brain injury

Quality of Life Research ◽

10.1007/s11136-021-02932-z ◽

2021 ◽

Author(s):

Isabel R. A. Retel Helmrich ◽

David van Klaveren ◽

Simone A. Dijkland ◽

Hester F. Lingsma ◽

Suzanne Polinder ◽

...

Keyword(s):

Quality Of Life ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Model Performance ◽

Prognostic Models ◽

Health Related Quality ◽

Mild Tbi ◽

Related Quality ◽

Health Related

Abstract Background Traumatic brain injury (TBI) is a leading cause of impairments affecting Health-Related Quality of Life (HRQoL). We aimed to identify predictors of and develop prognostic models for HRQoL following TBI. Methods We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Core study, including patients with a clinical diagnosis of TBI and an indication for computed tomography presenting within 24 h of injury. The primary outcome measures were the SF-36v2 physical (PCS) and mental (MCS) health component summary scores and the Quality of Life after Traumatic Brain Injury (QOLIBRI) total score 6 months post injury. We considered 16 patient and injury characteristics in linear regression analyses. Model performance was expressed as proportion of variance explained (R2) and corrected for optimism with bootstrap procedures. Results 2666 Adult patients completed the HRQoL questionnaires. Most were mild TBI patients (74%). The strongest predictors for PCS were Glasgow Coma Scale, major extracranial injury, and pre-injury health status, while MCS and QOLIBRI were mainly related to pre-injury mental health problems, level of education, and type of employment. R2 of the full models was 19% for PCS, 9% for MCS, and 13% for the QOLIBRI. In a subset of patients following predominantly mild TBI (N = 436), including 2 week HRQoL assessment improved model performance substantially (R2 PCS 15% to 37%, MCS 12% to 36%, and QOLIBRI 10% to 48%). Conclusion Medical and injury-related characteristics are of greatest importance for the prediction of PCS, whereas patient-related characteristics are more important for the prediction of MCS and the QOLIBRI following TBI.

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