Biology subjects

Dixon, C. E.

Publications and source records attributed to Dixon, C. E..

3 recordsLinked to original sources

bioRxiv2026

PRECISE TBI Model Catalog: Increasing Accessibility and Reproducibility in TBI research

Preclinical traumatic brain injury (TBI) research relies on experimental models that vary by mechanism, parameters, surgical procedures, species, strains, and ages, to name a few. While these models are crucial for understanding injury mechanisms and testing therapies, the progress in translating this knowledge to the clinic has been limited. This is in part due to fragmented resources and inconsistent reporting of critical variables. Here, we introduce the PRECISE-TBI model catalog, a centralized, queryable resource that consolidates metadata from published studies. The catalog integrates curated annotations from more than 450 papers, including details such as age, sex, strain, model type, device, and injury parameters. Where available, entries are also linked to protocols and datasets to enhance transparency and reproducibility. The Model Catalog serves as a living resource that enables cross-study comparison, identifies gaps in reporting, and connects the literature to datasets, protocols, device information, and other relevant resources. Analysis of the initial catalog entries revealed gaps in the reporting of device, age, and weight. In contrast, the reporting of sex improved over time, with over 90% of recent studies within the catalog papers reporting sex. Strain was also reported in most studies, with consistent reporting of specificity, especially for the C57 mice substrain. We expect the Model Catalog to serve as a valuable tool to enhance study design and reproducibility in preclinical TBI research while advancing FAIR data principles in the TBI field.

neuroscience↗

bioRxiv2023

Brain Injury Knowledge Ontology (BIKO) for traumatic brain injury: Formalizing concepts and methods used in translational traumatic brain injury research.

Traumatic brain injury (TBI) is an insult to the brain resulting from an external force and is a significant cause of morbidity and mortality in the United States. No effective clinical therapeutics currently exist for this injury. Although several therapies and procedures have been deemed successful for TBI treatment in preclinical research studies, they have yet to be translated into human patients. These discouraging results have left many scientists questioning the role of animal models in drug discovery for TBI. One major hurdle in translating the knowledge obtained in the laboratory to the clinic is the methodological variance across these studies. This variance can hinder the ability to draw conclusions from conflicting studies and aggregate data across various research studies, which ultimately impedes the ability to aggregate data across these studies. Therefore, addressing this variance is crucial for bridging the gap between the laboratory and the clinic. The increasing volume of papers and associated data being published every day makes this hurdle even more difficult to overcome. The initial steps to address these knowledge gaps are identifying these studies and creating a shared knowledge framework for mapping their terminology. We are developing the Brain Injury Knowledge Ontology (BIKO) to create a standardized model to describe methods and outcome measures used within preclinical and clinical TBI therapy studies to facilitate comparison across studies and models. The first version of BIKO focuses on modeling the major preclinical TBI models, e.g., Controlled Cortical Impact Model, Fluid Percussion Model, and Weight-Drop Model), major neurological injuries related to these models and their relationship to clinical pathophysiology. We show how BIKO provides a machine-readable way to represent the methodologies used in TBI therapeutic studies to compare models across clinically relevant features.

bioinformatics↗

bioRxiv2020

Spatial distribution of neuropathology and neuroinflammation elucidate the biomechanics of fluid percussion injury

Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. Finite element biomechanical models of diffuse brain injury predict regions of maximum stress and strain. However, the application of a skull with uniform thickness may mask the pathophysiology due to varying thickness of human and animal skulls. Force applied to the intact skull would diffuse the forces, whereas forces applied through an open skull are distributed along paths of least resistance within and then exiting the skull. We hypothesized that the local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology in underlying cortical tissue. We demonstrated local thickening of the skull at the temporal ridges using contour analysis of coronal skull sections and oblique sectioning on MRI. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge due to the material properties of the skull based on thickness, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge prior to injury reduced the injury-induced inflammation in sensorimotor cortex. These data build evidence for the temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy. HighlightsO_LIThe temporal ridge is 75% thicker than the adjacent skull of the rodent C_LIO_LIExperimental diffuse TBI neuropathology occurs beneath the length of the temporal ridge C_LIO_LINeuropathology encompasses sensorimotor cortex, somatosensory thalamus, and dorsolateral hippocampus C_LIO_LIProposed mechanism of biomechanical injury forces include the temporal ridge C_LI

neuroscience↗