The following project presents in silico investigation of axonal damage in Diffuse Axonal Injury (DAI). When axons face a shear force, orientation of the lipids in the axonal membrane gets disrupted. Depending on the value of the force, a tensile strain causes the axons to get partially or fully deformed and in some cases a pore forms in the membrane. Using Molecular Dynamic (MD) simulation and a coarse grain model, a series of bilayers with various bilayer structure (single bilayer, parallel bilayer and cylindrical bilayer) and similar composition to biological axonal membrane were simulated. This was initially done to investigate the strain rate dependency of the bilayers, and their viscoelastic ability on returning to their original shape from their deformed forms. To achieve this, various deformation velocities were applied to the bilayers reaching 20% strain and relaxing the bilayer after. Additionally, the bilayers were deformed further until they reached a pore. It was found that the bilayers can almost recover from their deformed forms to their original length when they were deformed at 20% strain level. In conjunction, no correlation between the deformation velocity and lipid deformation was observed. Further, it was found that bilayers with different lipid percentage to axonal bilayer has different strain values for water penetration and for pore formation. The strain value for cylindrical bilayer was found very high compared to the strain values found in vitro. The strain for pore formation of parallel and single bilayer was found to be around 80% to 90% and for water penetration was found to be 70% for single bilayer and 50% for parallel bilayer. A slight difference in strain for pore formation between single and parallel bilayer was found which showed the bilayer structure can play a role in simulation results. The effect of the length in the simulations results was also observed where shorter bilayers showed lower strain for pore formation compared to longer bilayers.

Die vorliegende Arbeit untersucht die aktuelle wissenschaftliche Evidenz zur Diagnostik und Therapie neuropsychologischer Störungen nach Hirnschädigung, wie sie bis 2020 in Leitlinien publiziert wurde. Deren Umsetzung ist nur möglich, wenn die institutionellen Rahmenbedingungen dies erlauben. Unter Einbezug der klinischen Erfahrung wurden daher auf Basis der Leitlinien Standards für eine wissenschaftlich fundierte neuropsychologische Diagnostik und Therapie erarbeitet. Es entstanden Best-Practice-Empfehlungen zu Strukturund Prozessqualität, insbesondere zu Intensität und Häufigkeit der Interventionen. Diese werden für die wichtigsten neuropsychologischen Funktionsbereiche vorgestellt. Sowohl die Deutsche Gesellschaft für Neuropsychologie e. V. (GNP) als auch die Deutsche Gesellschaft für Neurologie e. V. (DGN) unterstützen diese Empfehlungen. Sie richten sich an Neuropsycholog_innen sowie an Einrichtungsleitende und Sozialversicherungsträger und definieren die Rahmenbedingungen für eine auf den individuellen Fall angepasste leitliniengerechte neuropsychologische Behandlung. / Recent years have seen the establishment of evidence-based guidelines for neuropsychological diagnostics and therapy; however, implementing these guidelines depends on structures and processes necessary to enable essential aspects like therapy frequency and intensity. The present work examines the current scientific evidence for the neuropsychological treatment of traumatic and nontraumatic brain injury, as published in guidelines up to 2020. Standards for evidence-based neuropsychological diagnostics and therapy were developed on this basis, including clinical experience and additional literature research. Best-practice recommendations on both general and specific structural and process quality emerged, especially on the intensity and frequency of interventions. These are presented for the most important neuropsychological functional areas. The German Neuropsychological Society (GNP) and the German Society for Neurology (DGN) support these recommendations. They are aimed at neuropsychologists as well as facility managers and social insurance providers, and they define the framework for guideline-based neuropsychological treatment adapted to individual cases.

Background: Traumatic brain injury (TBI) still remains a difficult disorder to treat. TBI has been associated to chronic neuroinflammation and a high risk for neurodegenerative disorders. Since 2001 between ten to twenty percent of all deployed military members have suffered a combat-related TBI. Nearly twenty to thirty percent of those will experience chronic cognitive, behavioral and somatic symptoms after suffering a TBI. Methods: The objective of this review is to evaluate current literature examining vitamin D as a neurosteroid with protective properties and its clinical relevance after traumatic brain injury. Vitamin D is known to participate in neurobiological processes and genomic regulation in the brain. Clinical and laboratory findings support that vitamin D modulates the immune responses to trauma, diminishes oxidative and toxic damage, and inhibiting activation and progression of the neuroinflammation. Inadequate levels of vitamin D have been identified as a common risk factor for many neurological disorders and have been linked to poorer recovery. Results: This review found compelling evidence to support that the pathology of TBI is closely associated with neuroprotective mechanisms of vitamin D. Low vitamin D levels are common among US active duty military and veterans. The findings strongly suggest that optimizing vitamin D prior to injury could improve the recovery for military members after experiencing a TBI. Vitamin D ameliorates brain damage by modulating neuroinflammation, improving cell survival and down-regulating mechanisms involved in the progression of cell damage following a TBI. However, further studies are needed to evaluate the effects of vitamin D optimization in TBI outcomes.

Background: To reduce the reliance on clinical judgment for the regulation of sports-related traumatic brain injury, identifying and measuring objective to biofluid biomarkers can provide important insight into the diagnosis (Determining the type and origin of a disorder) and prognosis (Determining the chance of survival of a disorder) of SR-TBIs. A biomarker is a qualitative or quantitative measurement that provides a measure of a subject’s physiological or pathological condition at a specific time or during a disease state. Recent literature has suggested that biomarkers can help in the screening of patients exhibiting symptoms of mild traumatic brain injury (mTBI). Despite insights from recent research, it is not clear whether biomarkers and assessments of sports-related TBI are well-aligned. The objective of this study sought to review the current literature on predictive values of biomarkers: glial fibrillary acidic protein (GFAP), calcium channel binding protein S100 subunit beta (S100β), total-tau and neuron-specific enolase (NSE) for sports-related Traumatic Brain Injuries (SR-TBIs) to improve comprehension of biological and clinical contexts that can help evaluate the use of these biomarkers in sports-related TBIs and their potential function. Methods: The study was reported based on guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA: 2020 Edition) of 8 studies related to the assessment of biomarkers concerning SR-TBI. Literature searches were carried out on PubMed, Google Scholar, ScienceDirect, and ResearchGate. With an evidentiary table, the characteristics of the studies included in the meta-analysis (n = 14 studies) were presented. A significant role for biomarkers in the management of mild traumatic brain injury is suggested by the results of this analysis. From the literature, the significance of biomarkers in SR-TBI was identified along with the biomarkers that can facilitate more accurate clinical decision-making. Results:The initial search resulted in 73 articles, and the application of exclusion criteria and removal of duplicates resulted in the inclusion of 14 articles. Eight of the included studies were ([26], [27], [28], [30], [34], [39], [40], [41]), three were cohort studies ([25], [37], [45]) one was a pilot study [32], one interview, and an observational study [44]. The review was carried out to determine the efficacy of Biomarkers GFAP, S100β, Total-tau, and NSE to help in the screening of mild traumatic brain injury (mTBI) in patients showing symptoms. The focus is on athletes presenting at an emergency department with possible mTBI requiring a CT scan based on the application of a clinical algorithm. A forest plot was utilized, and the studies had low heterogeneity or variability (P Conclusions: It was established that the utility of biofluid biomarkers in the prediction of mild traumatic brain injury due to SRC is significant when the markers are used in large combinations. The four biofluid biomarkers (S100β, total-tau, GFAP, NSE) under study have strong predictive ability for mTBI, and their use can reduce the number of CT scans among TBI patients participating in athletic activities. Although preliminary evidence shows that other diagnostic treatments may help to mitigate traumatic brain injury sequelae, clinical trials are needed to further test their efficacy, specifically with diverse and high-risk populations. Luckily, the research on mTBI biomarkers is rapidly advancing, and should these biomarkers be better established clinically, they could easily hold many important roles.

This study presents mathematical surrogate models, derived from finite element kinematic response data, to predict car crash-induced occupant head and neck injury risk for a broad range of impact velocities (10 – 45 mph), impact locations, and angles of impact (-45° to 45°). The development of these models allowed for wide-scale injury prediction while significantly reducing the overall required number of impact test cases. From these, increases in both the impact velocity and the impact’s locational proximity to the occupant were determined to result in the greatest head and neck injury risks. Additionally, strong interactions between the impact orientation variables (location and angle) produced significant changes in the head injury risk, while the neck injury risk was relatively insensitive to these interactions; likely due to the uniaxiality of the current standard neck injury risk metrics. Overall, this methodology showed potential for future applications in wide-scale injury prediction or vehicular design optimization.

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