Establishment and Evaluation of a Novel High-efficiency Model of Graded Traumatic Brain Injury in Mice.

Abstract: Introduction Although previous studies have made significant contributions to establishment animal traumatic brain injury (TBI) models for simulation of human TBI, the accuracy, controllability, and modeling efficiency of animal TBI models need to be further improved. This study established a novel high-efficiency graded mice TBI model induced by shock wave. Methods A total of 125 mice were randomly divided into sham, 0.7mm, 0.6mm, and 0.5mm group according to the depth of the cross groove of the aluminum sheets. The stability and repeatability of apparatus were evaluated, and the integrity of blood-brain barrier (BBB), cerebral edema, neuropathological immunohistochemistry, apoptosis-related protein, and behavioral tests of neurological function were utilized to validate this new model. Results The results showed that four mice were injured simultaneously in one experiment, which were received by the same intensity of shock waves. Moreover, the mortality rates caused by three different aluminum sheets were consistent with the mortality rates of mild TBI, moderate TBI, and severe TBI. Compared with the sham group, mice in different injured groups significantly increased brain water content, BBB permeability, and neuronal apoptosis. And the mice in all injured groups showed poor motor ability, balancing, spatial learning and memory abilities. Conclusion The novel TBI apparatus has advantages in its small size, simple operation, high repeatability, high efficiency, and graded severity. Our TBI apparatus provides a novel tool to investigate the neuropathological changes and underlying mechanisms of TBI with various level of severities.