Abstract
The rat high-impact free weight drop model mimics the diffuse axonal injury caused by severe traumatic brain injury in humans, while severe controlled cortical impact can produce a severe traumatic brain injury model using precise strike parameters. In this study, we compare the pathological mechanisms and pathological changes between two rat severe brain injury models to identify the similarities and differences. The severe controlled cortical impact model was produced by an electronic controlled cortical impact device, while the severe free weight drop model was produced by dropping a 500 g free weight from a height of 1.8 m through a plastic tube. Body temperature and mortality were recorded, and neurological deficits were assessed with the modified neurological severity score. Brain edema and blood-brain barrier damage were evaluated by assessing brain water content and Evans blue extravasation. In addition, a cytokine array kit was used to detect inflammatory cytokines. Neuronal apoptosis in the brain and brainstem was quantified by immunofluorescence staining. Both the severe controlled cortical impact and severe free weight drop models exhibited significant neurological impairments and body temperature fluctuations. More severe motor dysfunction was observed in the severe controlled cortical impact model, while more severe cognitive dysfunction was observed in the severe free weight drop model. Brain edema, inflammatory cytokine changes and cortical neuronal apoptosis were more substantial and blood-brain barrier damage was more focal in the severe controlled cortical impact group compared with the severe free weight drop group. The severe free weight drop model presented with more significant apoptosis in the brainstem and diffused blood-brain barrier damage, with higher mortality and lower repeatability compared with the severe controlled cortical impact group. Severe brainstem damage was not found in the severe controlled cortical impact model. These results indicate that the severe controlled cortical impact model is relatively more stable, more reproducible, and shows obvious cerebral pathological changes at an earlier stage. Therefore, the severe controlled cortical impact model is likely more suitable for studies on severe focal traumatic brain injury, while the severe free weight drop model may be more apt for studies on diffuse axonal injury. All experimental procedures were approved by the Ethics Committee of Animal Experiments of Tianjin Medical University, China (approval No. IRB2012-028-02) in February 2012.