关键词:

 创伤性颅脑损伤, 神经功能障碍, 认知功能, 炎症反应, 免疫印迹法, 小鼠

Abstract:

Objective  To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI).    Methods  Totally 60 12-month-old Balb/c mice were divided into control group (10 in group) and TBI group (50 in group).TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting.    Results  Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium-binding adapter molecule 1(IBA1), chemokine C-X3-C-motif ligand1(CX3CL1), C-X3-C chemokine receptor 1(CX3CR1), NOD-like receptor thermal protein domain associated protein 3(NLRP3), and phosphorylation nuclear factor(p-NF)-κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p-Tau protein in the model group continued to increase at all time.   Conclusion  The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Key words: Traumatic brain injury, Neurological dysfunction, Cognitive function, Inflammation, Western blotting, Mouse