Accumulation of misfolded phosphorylated Tau (Tauopathy) can be triggered by mutations or by trauma, and is associated with synapse loss, gliosis, neurodegeneration and memory deficits. Fyn kinase physically associates with Tau and regulates subcellular distribution. Here, we assessed whether pharmacological Fyn inhibition alters Tauopathy. In P301S transgenic mice, chronic Fyn inhibition prevented deficits in spatial memory and passive avoidance learning. The behavioral improvement was coupled with reduced accumulation of phospho-Tau in the hippocampus, with reductions in glial activation and with recovery of presynaptic markers. We extended this analysis to a trauma model in which very mild repetitive closed head injury was paired with chronic variable stress over 2 weeks to produce persistent memory deficits and Tau accumulation. In this model, Fyn inhibition beginning 24 h after the trauma ended rescued memory performance and reduced phospho-Tau accumulation. Thus, inhibition of Fyn kinase may have therapeutic benefit in clinical Tauopathies.

Traumatic Brain Injury (TBI) remains a major cause of disability worldwide. It involves a complex neurometabolic cascade, including oxidative stress. The products of this manuscript is examining the underlying pathophysiological mechanism, including reactive oxygen species (ROS) and reactive nitrogen species (RNS). This process in turn leads to secondary injury cascade, which includes lipid peroxidation products. These reactions ultimately play a key role in chronic inflammation and synaptic dysfunction in a synergistic fashion. Although there are no FDA approved antioxidant therapy for TBI, there is a number of antioxidant therapies that have been tested and include free radical scavengers, activators of antioxidant systems, inhibitors of free radical generating enzymes, and antioxidant enzymes. Antioxidant therapies have led to cognitive and functional recovery post TBI, and they offer a promising treatment option for patients recovering from TBI. Current major challenges in treatment of TBI symptoms include heterogenous nature of injury, as well as access to timely treatment post injury. The inherent benefits of antioxidant therapies include minimally reported side effects, and relative ease of use in the clinical setting. The current review also provides a highlight of the more studied anti-oxidant regimen with applicability for TBI treatment with potential use in the real clinical setting.

Chronic Traumatic Encephalopathy (CTE) is a debilitating neurodegenerative disease, which has been increasingly reported in athletes, especially American football players, as well as military veterans in combat settings, commonly as a result of repetitive mild traumatic brain injuries (TBIs). CTE has a unique neuropathological signature comprised of accumulation of phosphorylated tau (p-tau) in sulci and peri-vascular regions, microgliosis, and astrocytosis. As per most recent disease classification, the disease manifests itself in four different stages, characterized by widespread tauopathy. Clinically, CTE has a more subtle presentation, as patients often present with two distinct phenotypes, with one subtype initially presenting with affective changes, and the other subtype with more cognitive impairment. On a genetic basis, there are no clear risk factor genes. Although ApoE4 carriers have been reported to suffer more severe outcome post TBI. As there are no disease modifying regimen for CTE, the newly developed TBI treatments, if administered in a time sensitive manner, can offer a potential viable option. Prevention is another key strategy that needs to be implemented in various sports and military settings. Providing education for safe practice techniques, such as safe tackling and hitting, and providing ready access to full neuropsychiatric assessment by team physician could have measurable benefits. The combination of advanced of research techniques including neuroimaging, as well as increasing public awareness of CTE, offers promising vistas for research advancement.

Purpose of review Over 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals. Recent findings Based on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients have good outcomes and disease modifying therapies do not increase the risk for severe disease. Viral infections and attendant neuroinflammation have been associated with the pathogenesis of Alzheimer's disease, Parkinson's disease, and MS, suggesting that COVID-19 may have the potential to incite or accelerate neurodegeneration. Summary Since patients with Alzheimer's disease are at higher risk for hospitalization and death in the setting of COVID-19, additional precautions and protective measures should be put in place to prevent infections and optimize management of comorbidities in this vulnerable population. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.

Comorbid post-traumatic stress disorder with traumatic brain injury (TBI) produce more severe affective and cognitive deficits than PTSD or TBI alone. Both PTSD and TBI produce long-lasting neuroinflammation, which may be a key underlying mechanism of the deficits observed in co-morbid TBI/PTSD. We developed a model of co-morbid TBI/PTSD by combining the closed head (CHI) model of TBI with the chronic variable stress (CVS) model of PTSD and examined multiple behavioral and neuroinflammatory outcomes. Male C57/Bl6 mice received sham treatment, CHI, CVS, CHI then CVS (CHI → CVS) or CVS then CHI (CVS → CHI). The CVS → CHI group had deficits in Barnes maze or active place avoidance not seen in the other groups. The CVS → CHI, CVS and CHI → CVS groups displayed increased basal anxiety level, based on performance on elevated plus maze. The CVS → CHI had impaired performance on Barnes Maze, and Active Place Avoidance. These performance deficits were strongly correlated with increased hippocampal Iba-1 level an indication of activated MP/MG. These data suggest that greater cognitive deficits in the CVS → CHI group were due to increased inflammation. The increased deficits and neuroinflammation in the CVS → CHI group suggest that the order by which a subject experiences TBI and PTSD is a major determinant of the outcome of brain injury in co-morbid TBI/PTSD.