Traumatic Brain Injuries during Development: Implications for Alcohol Abuse.
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ABSTRACT:
SUBMITTER: Weil ZM
PROVIDER: S-EPMC5517445 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:The high prevalence of traumatic brain injuries (TBI) among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI.We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption.Data were derived from the Centre for Addiction and Mental Health's 2013 Ontario Student Drug Use and Health Survey (OSDUHS). This population-based cross-sectional school survey included 10,272 7th to 12th graders (ages 11-20) who completed anonymous self-administered questionnaires in classrooms.Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed.Among all students, 22.4% (95% CI: 20.7, 24.1) reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year) TBI (45.5%, 95% CI: 41.0, 50.1). Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months). Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers.TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol mixed with energy drinks further increase the odds of TBI among adolescents. These associations warrant further investigation.
| S-EPMC4572704 | biostudies-other
Project description:Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.
| S-EPMC6890857 | biostudies-literature
Project description:Traumatic brain injury is among the leading causes of death in individuals under 45 years of age. However, since trauma mechanisms and survival times differ enormously, the exact mechanisms leading to the primary and secondary injury and eventually to death after traumatic brain injury (TBI) remain unclear. Several studies showed the versatile functions of microglia, the innate macrophages of the brain, following a TBI. Earlier being characterized as rather neurotoxic, neuroprotective capacities were recently demonstrated, therefore, making microglia one of the key players following TBI. Especially in cases with only short survival times, immediate microglial reactions are of great forensic interest in questions of wound age estimation. Using standardized immunohistochemical methods, we examined 8 cases which died causatively of TBI with survival times between minutes and 7 days and 5 control cases with cardiovascular failure as the cause of death to determine acute changes in microglial morphology and antigen expression after TBI. In this pilot study, we detected highly localized changes in microglial morphology already early after traumatic damage, e.g., activated microglia and phagocyted erythrocytes in the contusion areas in cases with minute survival. Furthermore, an altered antigen expression was observed with increasing trauma wound age, showing similar effects like earlier transcriptomic studies. There is minute data on the direct impact of shear forces on microglial morphology. We were able to show localization-depending effects on microglial morphology causing localized dystrophy and adjacent activation. While rodent studies are widespread, they fail to mimic the exact mechanisms in human TBI response. Therefore, more studies focusing on cadaveric samples need to follow to thoroughly define the mechanisms leading to cell destruction and eventually evaluate their forensic value.
| S-EPMC7578125 | biostudies-literature
Project description:BackgroundThe majority of clinical decision rules for prediction of intracranial injury in patients with mild traumatic brain injury (TBI) were developed from high-income countries. The application of these rules in low or middle-income countries, where the primary mechanism of injury was traffic accidents, is questionable.MethodsWe developed two practical decision rules from a secondary analysis of a multicenter, prospective cohort of 1,164 patients with mild TBI who visited the emergency departments from 2013 to 2016. The clinical endpoints were the presence of any intracranial injury on CT scans and the requirement of neurosurgical interventions within seven days of onset.ResultsThirteen predictors were included in both models, which were age ≥60 years, dangerous mechanism of injury, diffuse headache, vomiting >2 episodes, loss of consciousness, posttraumatic amnesia, posttraumatic seizure, history of anticoagulant use, presence of neurological deficits, significant wound at the scalp, signs of skull base fracture, palpable stepping at the skull, and GCS <15 at 2 hours. For the model-based score, the area under the receiver operating characteristic curve (AuROC) was 0.85 (95%CI 0.82, 0.87) for positive CT results and 0.87 (95%CI 0.83, 0.91) for requirement of neurosurgical intervention. For the clinical-based score, the AuROC for positive CT results and requirement of neurosurgical intervention was 0.82 (95%CI 0.79, 0.85) and 0.84 (95%CI 0.80, 0.88), respectively.ConclusionsThe models delivered good calibration and excellent discrimination both in the development and internal validation cohort. These rules can be used as assisting tools in risk stratification of patients with mild TBI to be sent for CT scans or admitted for clinical observation.
| S-EPMC7500687 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC.
2014-09-16 | GSE60753 | GEO
Project description:Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. Altered DNA methylation landscapes are ubiquitous features of cancer. Interpretation of epigenetic aberrations in HCC is confounded by effects of multiple etiologic drivers and underlying cirrhosis in most cases. We globally profiled the DNA methylome of 34 normal livers and 122 primary liver disease tissues arising in the setting of chronic hepatitis B (HBV) or C (HCV) viral infection, alcoholism (EtOH), and other causes to examine how these environmental agents impact DNA methylation in a manner that contributes to liver disease. Our results demonstrate that each etiologic factor leaves unique and overlapping signatures on the DNA methylome. CpGs aberrantly methylated in cirrhosis-HCV and conserved in HCC were enriched for cancer driver genes, suggesting a pathogenic role for HCV-induced methylation changes. Additionally, large genomic regions displaying stepwise hypermethylation or hypomethylation during disease progression were identified. HCC-HCV/EtOH methylomes overlap highly with cryptogenic HCC, suggesting shared epigenetically deregulated pathways for hepatic carcinogenesis. Finally, overlapping methylation abnormalities between primary and cultured tumors unveil highly conserved epigenetic signatures in HCC. Taken together, this study characterizes progressive liver DNA methylome changes under exposure to detrimental environmental agents and illuminates possible biomarkers for early detection of HCC. 156 primary tissues and 25 cultured normal and HCC cell lines
2014-09-16 | E-GEOD-60753 | biostudies-arrayexpress
Project description:Traumatic brain injuries (TBIs) are a leading cause of death and disability. Additionally, growing evidence suggests a link between TBI-induced neuroinflammation and neurodegenerative disorders. Treatments for TBI patients are limited, largely focused on rehabilitation therapy, and ultimately, fail to provide long-term neuroprotective or neurorestorative benefits. Because of the prevalence of TBI and lack of viable treatments, new therapies are needed which can promote neurological recovery. Cell-based treatments are a promising avenue because of their potential to provide multiple therapeutic benefits. Cell-based therapies can promote neuroprotection via modulation of inflammation and promote neurorestoration via induction of angiogenesis and neurogenesis. Neural stem/progenitor cell transplantations have been investigated in preclinical TBI models for their ability to directly contribute to neuroregeneration, form neural-like cells, and improve recovery. Mesenchymal stem cells (MSCs) have been investigated in clinical trials through multiple different routes of administration. Intravenous administration of MSCs appears most promising, demonstrating a robust safety profile, correlation with neurological improvements, and reductions in systemic inflammation following TBI. While still preliminary, evidence suggests cell-based therapies may become a viable treatment for TBI based on their ability to promote neuroregeneration and reduce inflammation.
| S-EPMC6826445 | biostudies-literature
Project description:Severe impacts to the head commonly lead to localized brain damage. Such impacts may also give rise to temporary pressure changes that produce secondary injuries in brain volumes distal to the impact site. Monitoring pressure changes in a clinical setting is difficult; detailed studies into the effect of pressure changes in the brain call for the development and use of animal models. The aim of this study is to characterize the pressure distribution in an animal model of penetrating traumatic brain injuries (pTBI). This data may be used to validate mathematical models of the animal model and to facilitate correlation studies between pressure changes and pathology. Pressure changes were measured in rat brains while subjected to pTBI for a variety of different probe velocities and shapes; pointy, blunt, and flat. Experiments on ballistic gel samples were carried out to study the formation of any temporary cavities. In addition, pressure recordings from the gel experiments were compared to values recorded in the animal experiments. The pTBI generated short lasting pressure changes in the brain tissue; the pressure in the contralateral ventricle (CLV) increased to 8 bar followed by a drop to 0.4 bar when applying flat probes. The pressure changes in the periphery of the probe, in the Cisterna Magna, and the spinal canal, were significantly less than those recorded in the CLV or the vicinity of the skull base. High-speed videos of the gel samples revealed the formation of spherically shaped cavities when flat and spherical probes were applied. Pressure changes in the gel were similar to those recorded in the animals, although amplitudes were lower in the gel samples. We concluded cavity expansion rate rather than cavity size correlated with pressure changes in the gel or brain secondary to probe impact. The new data can serve as validation data for finite element models of the trauma model and the animal and to correlate physical measurements with secondary injuries.
| S-EPMC4358068 | biostudies-literature
Project description:Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium-Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1 month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery-Åsberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected < 0.001, Cohen's d = 0.74) and 1 month (Pcorrected < 0.001, d = 2.20) after treatment and in PTSD (Pcorrected < 0.001, d = 2.54), depression (Pcorrected < 0.001, d = 2.80) and anxiety (Pcorrected < 0.001, d = 2.13) at 1 month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration: NCT04313712 .
| S-EPMC10878970 | biostudies-literature
Project description:Up to 10 million people per annum experience traumatic brain injury (TBI), 80-90% of which are categorized as mild. A hit to the brain can cause TBI, which can lead to secondary brain injuries within minutes to weeks after the initial injury through unknown mechanisms. However, it is assumed that neurochemical changes due to inflammation, excitotoxicity, reactive oxygen species, etc., that are triggered by TBI are associated with the emergence of secondary brain injuries. The kynurenine pathway (KP) is an important pathway that gets significantly overactivated during inflammation. Some KP metabolites such as QUIN have neurotoxic effects suggesting a possible mechanism through which TBI can cause secondary brain injury. That said, this review scrutinizes the potential association between KP and TBI. A more detailed understanding of the changes in KP metabolites during TBI is essential to prevent the onset or at least attenuate the severity of secondary brain injuries. Moreover, this information is crucial for the development of biomarker/s to probe the severity of TBI and predict the risk of secondary brain injuries. Overall, this review tries to fill the knowledge gap about the role of the KP in TBI and highlights the areas that need to be studied.
| S-EPMC10289013 | biostudies-literature