Modeling Traumatic Brain Injury: Assessing the State of the Science

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About this Research Topic

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Background

Traumatic brain injury (TBI) has received appropriately increased attention from funding agencies, academia and industry since the United States Congress began to significantly increase dedicated funding to this problem in 2007. Prior to 2007, clinicians and scientists focusing on TBI were relatively few and known to one another within the neurotrauma research community. Animal models of TBI were primarily oriented towards moderate and severe insults with impact being the most common mechanism. With increased funding came new models, new researchers and a new recognition that all TBIs are unique.

The dramatically increased focus on “mild” TBI, also referred to as concussion, has gone far to demonstrate the heterogeneity and complexity of brain injuries. As a research community, we have learned that we did not necessarily know very much about the complexity of these injuries-especially less severe injuries.

Along with the increased funding, new researchers and new knowledge, we have seen a significant broadening of animal models, including more recently models of blast induced neurotrauma that span the spectrum from open field blast to several versions of shock-tube generated trauma. The result has been a substantial increase in publications, sometimes with conflicting data using models that often cannot be compared to one another. In addition, little of this accrued knowledge from animal models has been translated into clinical solutions for humans.

The aim of this Research Topic is to pause and assess the current state of the science with regard to TBI animal models. We wish to assess: how existing models compare to the human condition with respect to causes and mechanisms; what are some of the major mechanistic and biological hurdles (such as differences in gene expression patterns in mouse vs human brain, and differences between lissencephalic and gyrencephalic brain anatomy), and how to overcome such hurdles, including pushing towards more chronic models of TBI and a potential greater engagement of small and large animals with gyrencephalic brains.

We welcome papers that address specific models at various levels of injury severity spanning the range from in vitro modeling to small and large animals, papers that compare and contrast mechanisms of injury among animal models and between animal models and the human brain, papers on novel models, and discussions of modeling chronic effects and co-morbidities of TBI. Manuscripts of research or thought exercises on improving animal-human injury translation are also welcomed. Manuscripts focusing on bioinformatics approaches such as common data elements for preclinical models and data repositories such as the FITBIR system for human TBI research are welcome, as are discussions of computational modeling of various mechanisms and scales of injury.

The goal of this Research Topic is to open a discussion and assessment of where we have been and where we would like to proceed as a field, including a more standardized, consistent, high-fidelity modeling of TBI across types of injury and on experimental animal species whose brains span a broad range of evolutionary complexity.

Keywords: TBI, Traumatic brain Injury, model, mechanism, method, blast, impact, state of the science, behavior

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