Abstract： Objective:A mouse model of traumatic brain injury（TBI）combined with seawater immersion hypothermia（SIH）was established by controlled cortical impact and low-temperature seawater immersion，and to observe the changes in vital signs and assess the degree of injury.Methods:The 48 male C57BL/6 mice were randomly divided into eight groups，i.e.，control group，TBI group，different water temperatures（10 ℃，15 ℃，and 20 ℃）seawater immersion groups，TBI combined with different water temperatures（10 ℃，15 ℃，and 20 ℃）seawater immersion groups，with six mice in each group. In the TBI group，the brain injury model was established by using a cortical impact device to strike the mouse cortex，while in the seawater immersion group，the mice were immersed below the clavicle in seawater at different temperatures and kept breathing unobstructed. In the control group，the mice were only grinded open the bone window，without any other treatment after hemostasis and suturing. The mortality rates of mice in each group after one，two，and three hours of low-temperature seawater immersion were observed，as well as the results of modified neurological severity score（mNSS）and Garcia score after 24 hours（one hour of low-temperature seawater immersion）were recorded. In the control group，the TBI group，the 15 ℃ seawater immersion group，and the TBI combined with 15 ℃ seawater immersion group after one hour of low-temperature seawater immersion，the blood gas indicators，brain tissue pathological change，and Evans blue（EB）contents of the mice were observed. The expression level of the ionized calcium binding adaptor molecule 1（Iba-l），a microglial cell marker，was detected by immunohistochemical staining.Results:The mortality rate of mice in the seawater immersion group and the TBI combined seawater immersion group increased with the decrease of water temperature after one hour of immersion（ P<0.05）. Compared with the control group，the mNSSs of the mice immersed in seawater at 10 ℃ and 15 ℃ increased significantly，while the Garcia score decreased significantly，with statistically significant differences（ P<0.01）. Compared with the TBI group，the mNSSs of the mice in the TBI combined with seawater immersion at different temperatures increased significantly，while the Garcia scores of the mice in the TBI combined with seawater immersion at 10 ℃ and 15 ℃ were significantly reduced，with statistically significant differences（ P<0.01）. After one hour of low-temperature seawater immersion，the arterial blood oxygen partial pressures（PaO 2）of the TBI group，the 15 ℃ seawater immersion group，and the TBI combined with 15℃ seawater immersion group mice were significantly reduced compared to that of the control group. At the same time，the arterial blood carbon dioxide partial pressure（PaCO 2）and blood oxygen saturation（SaO 2）of the TBI combined with 15 ℃ seawater immersion group mice were significantly reduced，compared to those of the control group；in the TBI combined with 15 ℃ seawater immersion group，the blood sodium，calcium，and chloride ion levels decreased significantly，while the glucose and lactate levels increased significantly；in the TBI group and the TBI combined with 15 ℃ seawater immersion group，the EB contents and Iba-1 level in the injured brain tissues of mice increased significantly，and those changes in the TBI combined with 15 ℃ seawater immersion group were more significant，with statistically significant differences（ P<0.05 or P<0.01）. Conclusion:The TBI combined with seawater immersion hypothermia mouse model is stable and reliable. Low temperature seawater immersion can damage the blood-brain barrier and worsen neurological damages.