A Systematic Review of Closed Head Injury Models of Mild Traumatic Brain Injury in Mice and Rats

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.

Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy

“…This model offers multiple advantages, which include the capacity to titrate the intensity of impact, depth of injury and duration of impact. Most critically, it does not involve craniotomy, thereby facilitating multiple mild injuries and reducing infectious complications [5].…”

Increased Behavioral Deficits and Inflammation in a Mouse Model of Co-Morbid Traumatic Brain Injury and Post-Traumatic Stress Disorder

“…Acoustic startle frequently measures the Vmax of the startle response. Previous studies by others showed acoustic startle response was inhibited in a variety of different TBI models (Sackheim et al, 2017;Teutsch et al, 2018;Bodnar et al, 2019). Therefore, the frequency of trials that had a Vmax of zero was assessed.…”

Chronic Neurobehavioral Impairments and Decreased Hippocampal Expression of Genes Important for Brain Glucose Utilization in a Mouse Model of Mild TBI

“…However, studying the chronic effects of mTBI is challenged by the lack of a suitable rodent model with prolonged symptoms similar to those in patients with mTBI. In most mTBI rodent models, the majority of behavioral abnormalities recover spontaneously within 3-4 weeks or have not been assessed for longer than that period (28)(29)(30)(31)(32). To establish an animal model of mTBI with neurobehavioral abnormalities that can last for months, we used repetitive mild closed head impacts to induce the brain injury in mice.…”