A Systematic Review of Closed Head Injury Models of Mild Traumatic Brain Injury in Mice and Rats
Summary & key facts
Researchers collected and organized what scientists have done to model mild traumatic brain injury (mTBI) in mice and rats. They searched two major scientific databases and followed standard rules for picking studies, then pulled together details on injury methods, the kinds of data researchers report, and the behavioral and brain-tissue outcomes. They compiled about 400 papers and found many different methods being used and important gaps, like too few female animals and too few very young or very old animals. The review is meant to help other researchers pick the best model for their question and to show what we still don’t know about mTBI.
- The authors searched two major databases of scientific papers and used an accepted checklist for systematic reviews to decide which studies to include.
- They gathered information from about 400 studies that used closed-head injuries described as mild in mice or rats.
- The review recorded details about how injuries were caused, what standard data were reported, and what behavioral tests and brain-tissue (histology) outcomes were measured.
- The studies use a wide variety of methods to create mild head injuries, so there is no single standard model used across the field.
- Female animals and both very young and very old animals were under-represented in the studies, meaning most work used male, adult rodents.
- The paper does not claim one model is best for human mild TBI. Instead, it provides a starting point to compare models and to find gaps where more research is needed.
Abstract
Mild TBI (mTBI) is a significant health concern. Animal models of mTBI are essential for understanding mechanisms, and pathological outcomes, as well as to test therapeutic interventions. A variety of closed head models of mTBI that incorporate different aspects (i.e., biomechanics) of the mTBI have been reported. The aim of the current review was to compile a comprehensive list of the closed head mTBI rodent models, along with the common data elements, and outcomes, with the goal to summarize the current state of the field. Publications were identified from a search of PubMed and Web of Science and screened for eligibility following PRISMA guidelines. Articles were included that were closed head injuries in which the authors classified the injury as mild in rats or mice. Injury model and animal-specific common data elements, as well as behavioral and histological outcomes, were collected and compiled from a total of 402 articles. Our results outline the wide variety of methods used to model mTBI. We also discovered that female rodents and both young and aged animals are under-represented in experimental mTBI studies. Our findings will aid in providing context comparing the injury models and provide a starting point for the selection of the most appropriate model of mTBI to address a specific hypothesis. We believe this review will be a useful starting place for determining what has been done and what knowledge is missing in the field to reduce the burden of mTBI.
