DNALI1 Promotes Neurodegeneration after Traumatic Brain Injury via Inhibition of Autophagosome-Lysosome Fusion.

Traumatic brain injury (TBI) leads to progressive neurodegeneration that may be caused by chronic traumatic encephalopathy (CTE). However, the precise mechanism remains unclear. Herein, the study identifies a crucial protein, axonemal dynein light intermediate polypeptide 1 (DNALI1), and elucidated its potential pathogenic role in post-TBI neurodegeneration. The DNALI1 gene is systematically screened through analyses of Aging, Dementia, and TBI studies, confirming its elevated expression both in vitro and in vivo. Moreover, it is observed that altered DNALI1 expression under normal conditions has no discernible effect. However, upon overexpression, DNALI1 inhibits autophagosome-lysosome fusion, reduces autophagic flux, and exacerbates cell death under pathological conditions. DNALI1 silencing significantly enhances autophagic flux and alleviates neurodegeneration in a CTE model. These findings highlight DNALI1 as a potential key target for preventing TBI-related neurodegeneration.

A Decision-Analytic Approach to Addressing the Evidence About Football and Chronic Traumatic Encephalopathy.

Doubts can be raised about almost any assertion that a particular exposure can lead to an increase in a given adverse health effect. Even some of the most well-accepted causal associations in public health, such as that linking cigarette smoking to increased lung cancer risk, have intriguing research questions remaining to be answered. The inquiry whether an exposure causes a disease is never wholly a yes/no question but ought to follow from an appraisal of the weight of evidence supporting the positive conclusion in light of any coherent theories casting doubt on this evidence and the data supporting these. More importantly, such an appraisal cannot be made sensibly without considering the relative consequences to public health and economic welfare of specific actions based on unwarranted credulity (false positives) versus unwarranted skepticism (false negatives). Here we appraise the weight of evidence for the premise that repeated head impacts (RHIs) in professional football can increase the incidence of chronic traumatic encephalopathy (CTE) and, in turn, cause a variety of cognitive and behavioral symptoms. We first dismiss four logical fallacies that should not affect the appraisal of the weight of evidence. We then examine four alternative hypotheses in which RHI is not associated with CTE or symptoms (or both), and we conclude that the chances are small that the RHI→ CTE→ symptoms link is coincidental or artifactual. In particular, we observe that there are many specific interventions for which, even under a skeptical appraisal of the weight of evidence, the costs of a false positive are smaller than the false negative costs of refusing to intervene.

Preventive potential of low intensity pulsed ultrasound for chronic traumatic encephalopathy after repetitive head collisions in contact sports.

Chronic traumatic encephalopathy (CTE), a disease process well-recognized in boxers, American football players and military personnel, is a progressive neurodegenerative disease caused by repetitive blows to the head. Subjects with CTE can have a wide range of emotional, cognitive and physical symptoms. The cognitive group patients had a significantly higher probability of developing dementia in later years. Currently, there are no disease modifying regimen for CTE. Timely intervention of head blow could diminish the development of CTE. Low-intensity pulsed ultrasound (LIPUS) is a common adjunct used to promote bone healing for fresh fracture. Recent reports suggest that LIPUS can noninvasively modulate the cortical function and have neuroprotective effect in various animal models of traumatic brain injury, stroke, Alzheimer's disease and major depressive disorder. The multifunctional mechanisms of LIPUS neuroprotective effect include several trophic factor stimulations, anti-inflammatory properties and reduction of brain edema. From the above evidence, LIPUS intervention could be a strategy for the prevention of the clinical CTE sequelae of repetitive head blows. We hypothesized that due to its neuroprotective effects, the non-invasive and easy-to-use method of LIPUS brain stimulation could have a preventive effect on players who have head blows during the match. The development of a time sensitive protocol, resembling the therapeutic algorithm for traumatic brain injury, would potentially prevent the development of subsequent CTE adverse outcome. Further long-term longitudinal studies of LIPUS stimulation are warranted to verify the prevention efficacy of this intervention for CTE.

Chronic traumatic encephalopathy in an epilepsy surgery cohort: Clinical and pathologic findings.

OBJECTIVE: To determine the occurrence of chronic traumatic encephalopathy (CTE) in young adult patients undergoing epilepsy surgery. METHODS: Ten patients who underwent epilepsy surgery were randomly selected for this retrospective study. The patients were 18-45 years of age, had preoperative neuropsychological evaluation, and had 1 year postoperative follow-up. Microscopic sections from resections were evaluated for the presence of CTE with standard stains and antibodies to tau (clone AT8). RESULTS: The median age at resection was 32.5 years (range 23-43) and the median duration of seizures was 23.5 years (range 3-28). Eight had a history of head injury. Preoperative neuropsychological testing showed mild to moderate cognitive impairment in 8 patients (80%). Pathologic examination in one patient showed focal sparse tau-immunoreactive lesions along descending rami and cortical gyral depths of the resected frontal lobe. Nine patients had no evidence of CTE. All focal cortical resections showed variable subpial and subcortical gliosis commonly identified in patients with chronic seizure disorders. CONCLUSIONS: The present small retrospective observational study suggests that CTE may occur, but appears uncommon, in young adult patients undergoing surgical treatment for drug-resistant focal epilepsy. The significance of these findings requires further investigation to define the relative importance of tau accumulation in younger adult patients with drug-resistant focal epilepsy and cognitive decline.

The chronic and evolving neurological consequences of traumatic brain injury.

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population.

Encefalopatía traumática crónica, definición, diagnóstico y prevención: revisión de la literatura / Chronic traumatic encephalopathy, definition, diagnosis and prevention: review of literature

La encefalopatía traumática crónica (ETC) es una enfermedad neurodegenerativa que se produce como consecuencia traumatismos cerebrales repetitivos; concusiones, que son un síndrome clínico que se caracteriza por una alteración de la función cerebral. Una concusión, bajo su estricta definición, no debiese causar cambios estructurales en el cerebro por lo que no sería visible a través de imágenes, sí existen cambios a nivel microscópicos, bioquímicos y biomecánicos. La mayoría de los pacientes tienen completa resolución de sus síntomas dentro de 10 días (90 por ciento), pero existe un pequeño porcentaje que persiste con estos, pudiendo presentarse como un síndrome postconcusional, síndrome de segundo impacto o una encefalopatía traumática crónica. La ETC se caracteriza por la acumulación de prot-tau hiperfosforilada en neuronas y astrocitos. Estas se van a presentar en forma de ovillos o hilos neurofibrilares. En etapas iniciales las encontraremos de forma focalizada en la corteza frontal y en las formas más severas su distribución será más generalizada, distribuyéndose en la mayoría de las regiones del cerebro. Su diagnóstico se realiza a través de histopatología, por lo que hasta el momento sólo se ha logrado post-mortem. Se está trabajando en nuevas tecnologías asociadas a biomarcadores y PET para lograr una diagnostico premortem. El mayor énfasis en el manejo de esta taupatía es la prevención y adecuado manejo de las concusiones.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease which is produced as a consequence of repeated brain trauma: concussions, which are a clinical syndrome characterized by an alteration in brain functions. A concussion, understrict definition, should not cause structural changes to the brain. Therefore, it would not be possible to see through images if there were changes at a microscopic, biochemical level. Most patients see their symptoms completely resolved within 10 days (90 percent), but there is a small percentage which persists, and these might cause a post-concussional syndrome, second impact syndrome of chronic traumatic encephalopathy. CTE is characterized by the accumulation of hyper-phosphorylated Tau protein in neurons and astrocytes. These appear in the form of neurofibrillary tangles. During the initial stages they are focalized in the frontal cortex and, in more severe cases, their distribution is more generalized, spreading through the majority of the regions in the brain. It is diagnosis is done through histopathology. Thus, it has only been possible to do post mortem. New technologies associated with bio-markers and PET are being worked on to achieve a pre-mortem diagnosis. The greatest emphasis in the handling of this tauopathy lies in the prevention and the adequate handling of concussions.