Multiple episodes of mild traumatic brain injury result in impaired cognitive performance in mice

Objectives: Results from recent studies on animal models of concussion suggest that multiple, rather than single, episodes of mild traumatic brain injury result in impaired cognitive performance in mice. The objective of the present study was to administer multiple impacts to the heads of mice while directly measuring the force of the impacts to determine how these parameters are related to transient loss of consciousness, cognitive deficits, and potential neuropathologic effects. Methods: Seven-week-old male C57BL/6 mice were randomly assigned to experimental conditions involving three impacts (weight-drop method) to the head to induce mild traumatic brain injury or to sham control procedures. Some impacted (n = 10) and sham control (n = 10) mice were evaluated behaviorally and tested for spatial learning using the Morris water maze (MWM), whereas other impacted (n = 10) and sham control (n = 5) mice were used for histopathologic analysis. Results: The mean (+/-SD) force of impact was 19 (+/-3.5) N. Impacted mice took longer to regain consciousness compared with sham control mice (p < 0.0005). Behavioral test results showed that the groups did not differ on activity or sensorimotor tests or during cued trials in the MWM. Impacted mice exhibited impaired spatial learning performance during place trials in the MWM (p < 0.05). Silver staining revealed a contra-coup type of injury involving ventral brain structures in contact with or in close proximity to the skull. Conclusions: This multiple-impact model, delivered within a specifiable force range, results in transient, reversible loss of consciousness, a contra-coup brain injury, and cognitive impairment.