Construction and evaluation of a simple and stable mouse model of traumatic brain injury

Objective To construct and evaluate a mouse model of traumatic brain injury (TBI) that simulates both motor and cognitive impairment. Methods Twenty-four healthy male C57BL/6 mice were randomly divided into a sham group and a TBI group (n=12/group). The TBI model was prepared by referring to the compression injury model with some modifications. The sham group underwent an identical process without mechanical trauma. Motor function was evaluated using the rotarod and beam-walking tasks at 1, 3, 7, 14, 21, 28 days post-injury. Spatial learning and memory capacities were assessed at 28, 29, 30, 31, 32, 33 days post-injury by the Morris Water Maze (MWM) test. Nissl staining was performed to observe pathological changes and immunofluorescence staining to detect the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor protein (Iba-1) in the mouse brain on the 34th day after modeling. Results The latency for the TBI group was significantly lower than that for the sham group, and the frequency of slipping off the beam by the right hindlimbs for the TBI group was significantly higher than that for the sham group at 1, 3, 7, 14, 21, 28 days post-injury (P<0.05). The escape latency for the TBI group was significantly longer than that for the sham group in the MWM test at 30, 31 and 32 days after modeling (P<0.05). The times of crossing the platform for the TBI group were significantly less than those for the sham group at day 33 after TBI (P< 0.05). The lesion volume for the sham group was significantly smaller than that for the TBI group [(0.55±0.06)% vs. (16.90±1.14)%, P<0.05]. The numbers of astrocytes in the TBI and sham groups were respectively 101.40±6.18/mm2 and 20.17±1.55/mm2, and the numbers of microglia in the 2 groups were respectively 119.20±6.28/mm2 and 23.58±1.72/mm2, showing statistically significant differences between the 2 groups (P<0.05). Conclusion Since the TBI model we constructed is simple and reproducible with stable motor deficits and cognitive impairments which are consistent with the pathological changes of moderate TBI, it can be used in animal TRI experiments. Key words: Traumatic brain injury; Model, animal; Movement deficit; Cognitive impairment